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bax activation by the bh3-only protein puma promotes cell dependence on antiapoptotic bcl-2 family members.it is still unclear whether the bh3-only protein puma (p53 up-regulated modulator of apoptosis) can prime cells to death and render antiapoptotic bh3-binding bcl-2 homologues necessary for survival through its ability to directly interact with proapoptotic bax and activate it. in this study, we provide further evidence, using cell-free assays, that the bh3 domain of puma binds bax at an activation site that comprises the first helix of bax. we also show that, in yeast, puma interacts with bax an ...200919380879
molecular cloning and functional characterization of two cyp619 cytochrome p450s involved in biosynthesis of patulin in aspergillus clavatus.patulin is an acetate-derived tetraketide mycotoxin produced by several fungal species, especially aspergillus, penicillium and byssochlamys species. the health risks due to patulin consumption by humans have led many countries to regulate it in human food. previous studies have shown the involvement of cytochrome p450 monooxygenases in the hydroxylation of two precursors of patulin, m-cresol and m-hydroxybenzylalcohol. in the present study, two cytochrome p450 genes were identified in the genom ...200919383676
shq1 is required prior to naf1 for assembly of h/aca small nucleolar and telomerase rnps.assembly of h/aca rnps in yeast is aided by at least two accessory factors, naf1p and shq1p. although the function of naf1p and its human ortholog naf1 has been delineated in detail, that of shq1p and its putative human ortholog shq1 remains obscure. we demonstrate that shq1 indeed functions in the biogenesis of human h/aca rnps and we dissect its mechanism of action. like naf1, shq1 binds the major h/aca core protein and pseudouridine synthase nap57 (aka dyskerin) but precedes the assembly role ...200919383767
dax-1 and sox6 molecular interplay results in an antagonistic effect in pre-mrna splicing.dax-1 (dss-ahc critical region on the x chromosome-1) is a member of the nuclear hormone receptor superfamily that has an important role in steroidogenesis and gonadogenesis. to investigate the role of dax-1 in the testis, a yeast two-hybrid screen was performed and sox6, member of the sry box (sox) protein family, was cloned as candidate. the interaction was confirmed biochemically and expression of sox6 overlapped with that of dax-1 in the developing gonad, as well as in sertoli cells of the a ...200919384854
mst4 and ezrin induce brush borders downstream of the lkb1/strad/mo25 polarization complex.the human lkb1 kinase, encoded by the ortholog of the invertebrate par4 polarity gene, is mutated in peutz-jeghers cancer syndrome. lkb1 activity requires complex formation with the pseudokinase strad and the adaptor protein mo25. the complex can induce complete polarization in a single isolated intestinal epithelial cell. we describe an interaction between mo25alpha and a human serine/threonine kinase termed mst4. a homologous interaction occurs in the yeast schizosaccharomyces pombe in the con ...200919386264
host responses to a versatile commensal: pamps and prrs interplay leading to tolerance or infection by candida albicans.the molecular interactions between commensal microorganisms and their host are basically different from those triggered by pathogens since they involve tolerance. when the commensal is genetically equipped to become an opportunistic pathogen, as is the case with candida albicans, the picture becomes more complex. in this case, the balance between protection and invasion depends on host reactivity to altered microbial expression of ligands interacting with innate immune sensors. based on experime ...200919388906
literature-based priors for gene regulatory networks.motivation: the use of prior knowledge to improve gene regulatory network modelling has often been proposed. in this article we present the first research on the massive incorporation of prior knowledge from literature for bayesian network learning of gene networks. as the publication rate of scientific papers grows, updating online databases, which have been proposed as potential prior knowledge in past research, becomes increasingly challenging. the novelty of our approach lies in the use of g ...200919389730
regulation of h3k4 trimethylation via cps40 (spp1) of compass is monoubiquitination independent: implication for a phe/tyr switch by the catalytic domain of set1.the multiprotein complex set1/compass is the founding member of the histone h3 lysine 4 (h3k4) methyltransferases, whose human homologs include the mll and hset1 complexes. compass can mono-, di-, and trimethylate h3k4, but transitioning to di- and trimethylation requires prior h2b monoubiquitination followed by recruitment of the cps35 (swd2) subunit of compass. another subunit, cps40 (spp1), interacts directly with set1 and is only required for transitioning to trimethylation. to investigate h ...200919398585
discovering structural cis-regulatory elements by modeling the behaviors of mrnas.gene expression is regulated at each step from chromatin remodeling through translation and degradation. several known rna-binding regulatory proteins interact with specific rna secondary structures in addition to specific nucleotides. to provide a more comprehensive understanding of the regulation of gene expression, we developed an integrative computational approach that leverages functional genomics data and nucleotide sequences to discover rna secondary structure-defined cis-regulatory eleme ...200919401680
a long-lasting, plasmin-activatable thrombin inhibitor aids clot lysis in vitro and does not promote bleeding in vivo.the leech protein hirudin is a potent inhibitor of thrombin, but clinical use of recombinant hirudin is restricted by haemorrhagic risks, and complicated by hirudin's rapid clearance from the circulation. we previously employed albumin fusion to slow hirudin variant 3 (hv3) clearance. in this study, we hypothesized that reconfiguration of the chimera, appending human serum albumin (hsa) to the n-terminus of hv3, with an intervening plasmin cleavage site, would create a slowly cleared, plasmin-ac ...200919404540
transcriptional activities of the pax6 gene eyeless regulate tissue specificity of ectopic eye formation in drosophila.pax genes encode dna binding proteins that play pivotal roles in the determination of complex tissues. members of one subclass, pax6, function as selector genes and play key roles in the retinal development of all seeing animals. mutations within the pax6 homologs including fly eyeless, mouse small eye and human pax6 lead to severe retinal defects in their respective systems. in drosophila eyeless and twin of eyeless, play non-redundant roles in the developing retina. one particularly interestin ...200919406113
frodos found: behold the cenp-a "ring" bearers.cenp-a is a histone h3-like protein specific to centromeres that is essential for kinetochore formation and accurate chromosome segregation in eukaryotes. recent studies (dunleavy et al., 2009; foltz et al., 2009; perpelescu et al., 2009; pidoux et al., 2009; williams et al., 2009) analyze cenp-a binding proteins required for the recruitment of cenp-a to centromeres in humans and in fission yeast, bringing us closer to understanding how centromere identity is faithfully propagated.200919410539
the secret message of heterochromatin: new insights into the mechanisms and function of centromeric and pericentric repeat sequence transcription.in the fission yeast, s. pombe, small dsrna generated by rnai-dependent mechanisms are involved in the establishment and maintenance of heterochromatic regions. the existence of conserved features within the general organization of centromeric and pericentromeric repeats in yeast, mouse and human argues in favor of a conserved role for centromeric and pericentromeric-derived transcripts across these species. in support of this, evidence is accumulating that centromeric and pericentromeric sequen ...200919412885
nutrient control of torc1, a cell-cycle regulator.it is well established that the target of rapamycin (tor) protein kinase has pivotal roles in controlling cell functions (including protein synthesis, cell growth and cell proliferation) and is implicated in numerous human diseases. mammalian tor complex 1 (mtorc1) signalling is activated by hormones and growth factors, and is also stimulated by intracellular amino acids. recent research has provided important new insight into the poorly understood mechanism by which amino acids activate mtorc1 ...200919419870
the dyslexia-associated protein kiaa0319 interacts with adaptor protein 2 and follows the classical clathrin-mediated endocytosis pathway.recently, genetic studies have implicated kiaa0319 in developmental dyslexia, the most common of the childhood learning disorders. the first functional data indicated that the kiaa0319 protein is expressed on the plasma membrane and may be involved in neuronal migration. further analysis of the subcellular distribution of the overexpressed protein in mammalian cells indicates that kiaa0319 can colocalize with the early endosomal marker early endosome antigen 1 (eea1) in large intracellular vesic ...200919419997
the yeast pif1 helicase prevents genomic instability caused by g-quadruplex-forming ceb1 sequences in vivo.in budding yeast, the pif1 dna helicase is involved in the maintenance of both nuclear and mitochondrial genomes, but its role in these processes is still poorly understood. here, we provide evidence for a new pif1 function by demonstrating that its absence promotes genetic instability of alleles of the g-rich human minisatellite ceb1 inserted in the saccharomyces cerevisiae genome, but not of other tandem repeats. inactivation of other dna helicases, including sgs1, had no effect on ceb1 stabil ...200919424434
expression of candida glabrata adhesins after exposure to chemical preservatives.adherence of candida glabrata, an opportunistic yeast pathogen, to host cells is mediated in part by the epa family of adhesins, which are encoded largely at subtelomeric loci, where they are subject to transcriptional silencing. in analyzing the regulation of the subtelomeric epa6 gene, we found that its transcription is highly induced after exposure to methylparaben, propylparaben, or sorbate. these weak acid-related chemicals are widely used as antifungal preservatives in many consumer goods, ...200919426114
assessing reliability of protein-protein interactions by integrative analysis of data in model organisms.protein-protein interactions play vital roles in nearly all cellular processes and are involved in the construction of biological pathways such as metabolic and signal transduction pathways. although large-scale experiments have enabled the discovery of thousands of previously unknown linkages among proteins in many organisms, the high-throughput interaction data is often associated with high error rates. since protein interaction networks have been utilized in numerous biological inferences, th ...200919426453
hset1: a novel approach for colon cancer therapy.histone-methyl transferases (hmts) are key enzymes that post-translationally modify histones, and serve key role in gene expression, epigenetic regulation, and as determinants of survival in malignant cells. recent studies have shed light on the role of hset1 which is a key element of highly conserved multi-protein hmt complex that catalyze methylation of histone h3 lysine 4 (h3k4) regulating expression of specific proteins important for the malignant phenotype. to understand the importance of d ...200919426701
n-acetyl cysteine protects against ionizing radiation-induced dna damage but not against cell killing in yeast and mammals.ionizing radiation (ir) induces dna strand breaks leading to cell death or deleterious genome rearrangements. in the present study, we examined the role of n-acetyl-l-cysteine (nac), a clinically proven safe agent, for it's ability to protect against gamma-ray-induced dna strand breaks and/or dna deletions in yeast and mammals. in the yeast saccharomyces cerevisiae, dna deletions were scored by reversion to histidine prototrophy. human lymphoblastoid cells were examined for the frequency of gamm ...200919427509
a novel recombinant human lactoferrin augments the bcg vaccine and protects alveolar integrity upon infection with mycobacterium tuberculosis in mice.lactoferrin, an iron binding glycoprotein, possesses multiple immune modulatory activities, including the ability to promote antigen specific cell-mediated immunity. previous studies showed that adding bovine lactoferrin to the bcg vaccine (an attenuated strain of mycobacterium bovis bacillus calmette guerin) resulted in increased host protective responses upon subsequent challenge with virulent erdman mycobacterium tuberculosis (mtb) in mice. the studies outlined here investigate utility of a n ...200919428915
a novel member of solute carrier family 25 (slc25a42) is a transporter of coenzyme a and adenosine 3',5'-diphosphate in human mitochondria.mitochondrial carriers are a family of proteins that transport metabolites, nucleotides, and cofactors across the inner mitochondrial membrane thereby connecting cytosolic and matrix functions. the essential cofactor coenzyme a (coa) is synthesized outside the mitochondrial matrix and therefore must be transported into mitochondria where it is required for a number of fundamental processes. in this work we have functionally identified and characterized slc25a42, a novel human member of the mitoc ...200919429682
decapping is preceded by 3' uridylation in a novel pathway of bulk mrna turnover.both end structures of eukaryotic mrnas, namely the 5' cap and 3' poly(a) tail, are necessary for transcript stability, and loss of either is sufficient to stimulate decay. mrna turnover is classically thought to be initiated by deadenylation, as has been particularly well described in saccharomyces cerevisiae. here we describe two additional, parallel decay pathways in the fission yeast schizosaccharomyces pombe. first, in fission yeast mrna decapping is frequently independent of deadenylation. ...200919430462
expression of hepatitis b surface antigen s domain in recombinant saccharomyces cerevisiae using gal1 promoter.hepatitis b virus, a member of the hepadnavirus family, causes the acute and chronic diseases of the human liver. the s domain of hepatitis b virus surface antigen (shbsag) was expressed under the control of the galactose-inducible gal1 promoter in recombinant saccharomyces cerevisiae. batch fermentation of s. cerevisiae 2805/pdeltamfalpha-shbsag resulted in 4.92gl(-1) dry cell mass and 2.21mgl(-1) shbsag concentration. to improve the expression level of shbsag, the pdi1 gene encoding protein di ...200919433220
[hev capsid protein interacts with cyp 2a6 and decreases its coumarin 7-hydroxylation activity].e2 is a recombinant hepatitis e virus capsid protein including its main antigenic determinants but lacking of the particle assembling domain. p239 was the c-terminal extending protein of e2 and could self-assemble to form virus like particles, which might serve as mimicry of virions both structurally and antigenically. we previously used yeast two-hybrid system to screen proteins interacting with e2 based on a human hepatocyte cdna library. one candidate was identified as the segment (aa388-437) ...200919437879
prl-3 promotes epithelial mesenchymal transition by regulating cadherin directly.prl-3 is a key gene associated with progression and metastasis of colorectal cancer. recently prl-3 was suggested to promote epithelial mesenchymal transition (emt) by downregulating e-cadherin expression. but the mechanisms of emt induced by prl-3 remain largely unknown. here we found that prl-3 could also promote emt in a colorectal cancer cell model sw480 with deficient e-cadherin expression in vivo and in vitro. prl-3 stable overexpression or knockdown sw480 cells were injected subcutaneousl ...200919440036
hares and tortoises: the high- versus low-throughput proteomic race.the analysis of the proteome can be undertaken with parallel, high-throughput techniques or those that analyze proteins in a serial, one-at-a-time manner. the former include 2-d gels and shotgun ms/ms; the latter includes libraries containing fusion proteins (gst, green fluorescent protein, tap-tag and others) that are engineered onto each protein in a proteome and then studied one by one. in this review, we explore the progress that these scientifically contrasting paradigms have made in measur ...200919441020
the search for a human holliday junction resolvase.four-way dna intermediates, known as holliday junctions, are formed during mitotic and meiotic recombination, and their efficient resolution is essential for proper chromosome segregation. bacteria, bacteriophages and archaea promote holliday junction resolution by the introduction of symmetrically related nicks across the junction, in reactions mediated by holliday junction resolvases. in 2008, after a search that lasted almost 20 years, a holliday junction resolvase was identified in humans. t ...200919442245
plasmodial aspartyl-trna synthetases and peculiarities in plasmodium falciparum.distinctive features of aspartyl-transfer rna (trna) synthetases (asprs) from the protozoan plasmodium genus are described. these apicomplexan asprss contain 29-31 amino acid insertions in their anticodon binding domains, a remarkably long n-terminal appendix that varies in size from 110 to 165 amino acids and two potential initiation codons. this article focuses on the atypical functional and structural properties of plasmodium falciparum cytosolic asprs, the causative parasite of human malaria ...200919443655
what was the set of ubiquitin and ubiquitin-like conjugating enzymes in the eukaryote common ancestor?ubiquitin (ub)-conjugating enzymes (e2) are key enzymes in ubiquitination or ub-like modifications of proteins. we searched for all proteins belonging to the e2 enzyme super-family in seven species (homo sapiens, mus musculus, drosophila melanogaster, caenorhabditis elegans, schizosaccharomyces pombe, saccharomyces cerevisiae, and arabidopsis thaliana) to identify families and to reconstruct each family's phylogeny. our phylogenetic analysis of 207 genes led us to define 17 e2 families, with 37 ...200919452197
artificial beta-defensin based on a minimal defensin template.we have designed and chemically synthesized an artificial beta-defensin based on a minimal template derived from the comparative analysis of over 80 naturally occurring sequences. this molecule has the disulfide-bridged beta-sheet core structure of natural beta-defensins and shows a robust salt-sensitive antimicrobial activity against bacteria and yeast, as well as a chemotactic activity against immature dendritic cells. an sar (structure-activity relationship) study using two truncated fragment ...200919453294
inhibitor of nuclear factor-kappab alpha derepresses hypoxia-inducible factor-1 during moderate hypoxia by sequestering factor inhibiting hypoxia-inducible factor from hypoxia-inducible factor 1alpha.hypoxia and inflammation often develop concurrently in numerous diseases, and both hypoxia-inducible factor (hif)-1alpha and nuclear factor-kappab (nf-kappab) are key transcription factors of stress response genes. an nf-kappab inhibitor, inhibitor of nf-kappab alpha (ikappab alpha), was found to interact with factor inhibiting hif (fih) and to be hydroxylated by fih. however, fih did not functionally regulate ikappab alpha, and the consequence of the fih-ikappab alpha interaction thus remains u ...200919456861
schizosacharomyces pombe rna polymerase ii at 3.6-a resolution.the second structure of a eukaryotic rna polymerase ii so far determined, that of the enzyme from the fission yeast schizosaccharomyces pombe, is reported here. comparison with the previous structure of the enzyme from the budding yeast saccharomyces cerevisiae reveals differences in regions implicated in start site selection and transcription factor interaction. these aspects of the transcription mechanism differ between s. pombe and s. cerevisiae, but are conserved between s. pombe and humans. ...200919458260
regenerative medicine bioprocessing: concentration and behavior of adherent cell suspensions and pastes.regenerative medicines based on human cells demand their harvesting, culture, and processing. manufacturing processes are likely to include cell concentration and subsequent controlled dosing of concentrates, for example, to the patient or tissue construct. the integrity and functionality of the cells must be maintained during these processing stages. in this study the performance of two different cell concentration protocols (involving centrifugation and resuspension) are compared and considera ...200919459141
[overexpression, purification and helicase activity analysis of recombinant human pif1 protein].pif1 subfamily helicase is conserved from yeast to humans with a lot of cellular functions. in order to elucidate the function of human pif1 helicase from biochemical level, we cloned human pif1 gene by pcr from hela cell cdna library. we co-transformed a pmstrna1 plasmid encoding rare trna codons and a plasmid encoding molecular chaperon to greatly enhance the overexpression of human pif1 protein. finally we purified full-length pif1 helicase by column chromatograph carried out at 4 degrees c u ...200919459334
evidence that ct694 is a novel chlamydia trachomatis t3s substrate capable of functioning during invasion or early cycle development.chlamydia trachomatis is an obligate intracellular parasite, occupies a membrane-bound vacuole throughout development and is capable of manipulating the eukaryotic host by translocating effector molecules via a type iii secretion system (t3ss). the infectious chlamydial elementary body (eb) is metabolically inactive yet possesses a functional t3s apparatus capable of translocating effector proteins into the host cell to facilitate invasion and other early cycle events. we present evidence here t ...200919460098
candida albicans cas5, a regulator of cell wall integrity, is required for virulence in murine and toll mutant fly models.candida albicans is the most common human fungal pathogen, yet the pathogenesis of c. albicans infection remains incompletely understood. we hypothesized that c. albicans has developed evolutionarily conserved mechanisms to invade disparate hosts and tested whether toll mutant flies could serve as a model host for high-throughput screening of c. albicans virulence genes. we screened 34 c. albicans mutants defective in putative transcription factor genes (see http://www.tigr.org/tigr-scripts/e2k1 ...200919463063
thromboxane a2-induced signal transduction is negatively regulated by kiaa1005 that directly interacts with thromboxane a2 receptor.thromboxane a(2) (txa(2)), a potent inducer of platelet aggregation and smooth muscle contraction, exerts its action through txa(2) receptor (tp). there are two alternative splicing variants of tp, tp alpha and tp beta. to clarify the signal transduction of tp pathway, we searched for putative tp binding proteins using a yeast two-hybrid system with the c-terminal region of tp alpha or tp beta as bait. we found kiaa1005 as a novel interacting protein of the tp alpha and tp beta c-terminal region ...200919464661
genome sequence of the recombinant protein production host pichia pastoris.the methylotrophic yeast pichia pastoris is widely used for the production of proteins and as a model organism for studying peroxisomal biogenesis and methanol assimilation. p. pastoris strains capable of human-type n-glycosylation are now available, which increases the utility of this organism for biopharmaceutical production. despite its biotechnological importance, relatively few genetic tools or engineered strains have been generated for p. pastoris. to facilitate progress in these areas, we ...200919465926
solution structure of s. cerevisiae pdcd5-like protein and its promoting role in h(2)o(2)-induced apoptosis in yeast.human pdcd5 protein is a novel programmed cell death-promoting molecule. however, the function of ymr074cp, a s. cerevisiae homologue of hpdcd5, is still unknown. heteronuclear nmr methods were used to determine the solution structure of the n-terminal 116-residue fragment (n116) of ymr074cp protein. n116 is shown to be a heterogeneous ensemble of flexibly folded conformations, adopting an extended triple-helix bundle fold that is connected to a mobile but structured alpha-helix in the n-terminu ...200919469552
biotechnological synthesis of the designer drug metabolite 4'-hydroxymethyl-alpha-pyrrolidinohexanophenone in fission yeast heterologously expressing human cytochrome p450 2d6--a versatile alternative to multistep chemical synthesis.1-(4-methylphenyl)-2-pyrrolidin-1-ylhexan-1-one (4'-methyl-alpha-pyrrolidinohexanophenone, mphp) is a new designer drug that appeared on the illicit drug market. it is mainly metabolized to 4'-hydroxymethyl-alpha-pyrrolidinohexanophenone (ho-mphp) followed by oxidation to the respective carboxylic acid. for studies on the quantitative involvement of human cytochrome p450 (cyp) isoenzymes in the initial hydroxylation, a reference standard of ho-mphp was needed. therefore, the aim of this study wa ...200919470220
mouse models of altered protein kinase a signaling.protein kinase a (pka) is an evolutionarily conserved protein which has been studied in model organisms from yeast to man. although the camp-pka signaling system was the first mammalian second messenger system to be characterized, many aspects of this pathway are still not well understood. owing to findings over the past decade implicating pka signaling in endocrine (and other) tumorigenesis, there has been renewed interest in understanding the role of this pathway in physiology, particularly as ...200919470615
tax1 enhances cancer cell proliferation via ras-raf-mek-erk signaling pathway.erbin is an erbb2 binding protein, which belongs to the lap (leucine-rich repeat (lrr) and pdz domain) protein family. we previously reported that tax1, a protein of the human t-cell leukemia virus type i (htlv-i), associated with erbin by using erbin pdz domain as a bait to screen a human t lymphocyte cdna library by a yeast two hybrid strategy. in the present study, we demonstrated that tax1 enhances cancer cell proliferation via ras-raf-mek-erk signaling pathway by using molecular section str ...200919472191
small rnas derived from snornas.small nucleolar rnas (snornas) guide rna modification and are localized in nucleoli and cajal bodies in eukaryotic cells. components of the rna silencing pathway associate with these structures, and two recent reports have revealed that a human and a protozoan snorna can be processed into mirna-like rnas. here we show that small rnas with evolutionary conservation of size and position are derived from the vast majority of snorna loci in animals (human, mouse, chicken, fruit fly), arabidopsis, an ...200919474147
an additional role for sumo in ubiquitin-mediated proteolysis.although the post-translational modification of proteins with small ubiquitin-like modifier (sumo) has a role in many biological processes, it was thought that sumo, unlike ubiquitin, does not target proteins for degradation. however, these views need to be revised, as recent findings in yeast and human cells indicate that sumo can act as a signal for the recruitment of e3 ubiquitin ligases, which leads to the ubiquitylation and degradation of the modified protein.200919474794
mitofusins and opa1 mediate sequential steps in mitochondrial membrane fusion.mitochondrial fusion requires the coordinated fusion of the outer and inner membranes. three large gtpases--opa1 and the mitofusins mfn1 and mfn2--are essential for the fusion of mammalian mitochondria. opa1 is mutated in dominant optic atrophy, a neurodegenerative disease of the optic nerve. in yeast, the opa1 ortholog mgm1 is required for inner membrane fusion in vitro; nevertheless, yeast lacking mgm1 show neither outer nor inner membrane fusion in vivo, because of the tight coupling between ...200919477917
family classification without domain chaining.motivation: classification of gene and protein sequences into homologous families, i.e. sets of sequences that share common ancestry, is an essential step in comparative genomic analyses. this is typically achieved by construction of a sequence homology network, followed by clustering to identify dense subgraphs corresponding to families. accurate classification of single domain families is now within reach due to major algorithmic advances in remote homology detection and graph clustering. howe ...200919478015
region of elongation factor 1a1 involved in substrate recognition by legionella pneumophila glucosyltransferase lgt1: identification of lgt1 as a retaining glucosyltransferase.lgt1 is one of the glucosyltransferases produced by the gram-negative bacterium legionella pneumophila. this enzyme modifies eukaryotic elongation factor 1a (eef1a) at serine 53, which leads to inhibition of protein synthesis and death of target cells. here we studied the region of eef1a, which is essential for substrate recognition by lgt1. we report that the decapeptide (50)gkgsfkyawv(59) of eef1a is efficiently modified by lgt1. this peptide covers the loop of the helix-loop-helix region form ...200919478083
a novel human nata nalpha-terminal acetyltransferase complex: hnaa16p-hnaa10p (hnat2-hard1).protein acetylation is among the most common protein modifications. the two major types are post-translational nepsilon-lysine acetylation catalyzed by kats (lysine acetyltransferases, previously named hats (histone acetyltransferases) and co-translational nalpha-terminal acetylation catalyzed by nats (n-terminal acetyltransferases). the major nat complex in yeast, nata, is composed of the catalytic subunit naa10p (n alpha acetyltransferase 10 protein) (ard1p) and the auxiliary subunit naa15p (n ...200919480662
[anti-glycan antibodies establish an unexpected link between c. albicans and crohn disease].almost 80 % of the dry weight of the yeast cell wall is composed of glycans including mannans, glucans and chitin. within this variable and complex edifice, glycans play a major role in their relation with the environment. experimental antibodies allowed to define the localization, the variability of expression and the biological role of numerous natural oligosaccharidic sequences. these glycans and their synthetic analogues were used to study the human humoral response during invasive candidias ...200919480828
dynamics of the spindle pole body of the pathogenic yeast cryptococcus neoformans examined by freeze-substitution electron microscopy.cryptococcus neoformans is an opportunistic human pathogen belonging to basidiomycetous fungi and has unique properties in cell cycle progression. in the present study, dynamics of the spindle pole body (spb) during the cell cycle was examined using freeze-substitution and serial thin-sectioning electron microscopy. the spb was located on the outer nuclear envelope and appeared either dumbbell- or bar-shaped in g1 through g2 phases. at the beginning of prophase, globular elements of the spb enla ...200919486162
laminin-511 and fibronectin degradation with candida yeast.the invasion mechanism of candida yeast is still partly unknown. in this study, we tested the ability of different commensal candida yeast to degrade two basement membrane and extracellular matrix proteins: laminin-511 (lm-511) and plasma fibronectin.200919486268
multivesicular endosome biogenesis in the absence of escrts.the endosomal sorting complex required for transport (escrt) protein machinery comprises four complexes, escrt-0, escrt-i, escrt-ii and escrt-iii, that facilitate receptor sorting into the lumen of multivesicular endosomes (mves) in order to terminate signalling receptors for final degradation within the lysosomes. even though escrt proteins appear to be essential for the biogenesis of mves in saccharomyces cerevisae, it is not clear whether escrt-independent pathways for mve biogenesis exist in ...200919490536
suppression of rft1 expression does not impair the transbilayer movement of man5glcnac2-p-p-dolichol in sealed microsomes from yeast.to further evaluate the role of rft1 in the transbilayer movement of man(5)glcnac(2)-p-p-dolichol (m5-dlo), a series of experiments was conducted with intact cells and sealed microsomal vesicles. first, an unexpectedly large accumulation (37-fold) of m5-dlo was observed in rft1-depleted cells (yg1137) relative to glc(3)man(9)glcnac(2)-p-p-dol in wild type (ss328) cells when glycolipid levels were compared by fluorophore-assisted carbohydrate electrophoresis analysis. when sealed microsomes from ...200919494107
identification and characterisation of a novel anti-viral peptide against avian influenza virus h9n2.avian influenza viruses (aiv) cause high morbidity and mortality among the poultry worldwide. their highly mutative nature often results in the emergence of drug resistant strains, which have the potential of causing a pandemic. the virus has two immunologically important glycoproteins, hemagglutinin (ha), neuraminidase (na), and one ion channel protein m2 which are the most important targets for drug discovery, on its surface. in order to identify a peptide-based virus inhibitor against any of ...200919497129
new atpase regulators--p97 goes to the pub.the conserved eukaryotic aaa-type atpase complex, known as p97 or vcp in mammals and cdc48 in yeast, is involved in a number of cellular pathways, including fusion of homotypic membranes, protein degradation, and activation of membrane-bound transcription factors. most likely, p97 is directed to this broad spectrum of cellular functions through its binding to specific cofactors. more than 20 different p97 cofactors have been described to date and our understanding of their cellular functions is ...200919497384
identification of autophagy genes in ciona intestinalis: a new experimental model to study autophagy mechanism.programmed cell death (pcd) is a mechanism implicated in many physiological and pathological processes. until recently, apoptosis (self-killing) was the most largely studied mechanism of pcd but a growing number of laboratories are now interested in autophagy (self-eating). in the past few years data showing a tight link between both pathways has accumulated. until now our laboratory used ciona intestinalis, a chordate model in which in vivo experiments are possible, to study apoptosis. recently ...200919502774
the c-terminal domain of cenp-c displays multiple and critical functions for mammalian centromere formation.cenp-c is a fundamental component of functional centromeres. the elucidation of its structure-function relationship with centromeric dna and other kinetochore proteins is critical to the understanding of centromere assembly. cenp-c carries two regions, the central and the c-terminal domains, both of which are important for the ability of cenp-c to associate with the centromeric dna. however, while the central region is largely divergent in cenp-c homologues, the c-terminal moiety contains two re ...200919503796
systematic study of protein sumoylation: development of a site-specific predictor of sumosp 2.0.protein sumoylation is an important reversible post-translational modification on proteins, and orchestrates a variety of cellular processes. recently, computational prediction of sumoylation sites has attracted much attention for its cost-efficiency and power in genomic data mining. in this work, we developed sumosp 2.0, an accurate computing program with an improved group-based phosphorylation scoring algorithm. our analysis demonstrated that sumosp 2.0 has greater prediction accuracy than sum ...200919504496
combined therapy with amphotericin b and caspofungin in an experimental model of disseminated histoplasmosis.to assess the effect of amphotericin b and caspofungin, as well as their combinations in the therapy of experimental disseminated histoplasmosis.200919507469
yip1a regulates the copi-independent retrograde transport from the golgi complex to the er.yip1a, a mammalian homologue of yeast yip1p, is a multi-spanning membrane protein that is considered to be involved in transport between the endoplasmic reticulum (er) and the golgi. however, the precise role of yip1a in mammalian cells remains unclear. we show here that endogenous yip1a is localized to the er-golgi intermediate compartment (ergic). knockdown of yip1a by rnai did not induce morphological changes in the golgi, er, or ergic. by analyzing a number of intracellular transport pathway ...200919509059
functional role for senataxin, defective in ataxia oculomotor apraxia type 2, in transcriptional regulation.ataxia oculomotor apraxia type 2 (aoa2) is an autosomal recessive neurodegenerative disorder characterized by cerebellar ataxia and oculomotor apraxia. the gene mutated in aoa2, setx, encodes senataxin, a putative dna/rna helicase which shares high homology to the yeast sen1p protein and has been shown to play a role in the response to oxidative stress. to investigate further the function of senataxin, we identified novel senataxin-interacting proteins, the majority of which are involved in tran ...200919515850
structural and functional divergence within the dim1/ksga family of rrna methyltransferases.the enzymes of the ksga/dim1 family are universally distributed throughout all phylogeny; however, structural and functional differences are known to exist. the well-characterized function of these enzymes is to dimethylate two adjacent adenosines of the small ribosomal subunit in the normal course of ribosome maturation, and the structures of ksga from escherichia coli and dim1 from homo sapiens and plasmodium falciparum have been determined. to this point, no examples of archaeal structures ha ...200919520088
role of picln in methylation of sm proteins by prmt5.picln is an essential, highly conserved 26-kda protein whose functions include binding to sm proteins in the cytoplasm of human cells and mediating the ordered and regulated assembly of the cell's rna-splicing machinery by the survival motor neurons complex. picln also interacts with prmt5, the enzyme responsible for generating symmetric dimethylarginine modifications on the carboxyl-terminal regions of three of the canonical sm proteins. to better understand the role of picln in these cellular ...200919520849
a genome-wide screen for regulators of torc1 in response to amino acid starvation reveals a conserved npr2/3 complex.torc1 is a central regulator of cell growth in response to amino acid availability, yet little is known about how it is regulated. here, we performed a reverse genetic screen in yeast for genes necessary to inactivate torc1. the screen consisted of monitoring the expression of a torc1 sensitive gfp-based transcriptional reporter in all yeast deletion strains using flow cytometry. we find that in response to amino acid starvation, but not to carbon starvation or rapamycin treatment, cells lacking ...200919521502
influenza a virus matrix protein 1 interacts with htfiiic102-s, a short isoform of the polypeptide 3 subunit of human general transcription factor iiic.influenza a virus matrix protein 1 (m1) is a multifunctional protein that plays important roles during replication, assembly and budding of the virus. to search for intracellular protein components that interact with m1 protein and explore the potential roles of these interactions in the pathogenesis of influenza virus infection, 11 independent proteins, including htfiiic102-s protein, encoding a short isoform of the tfiiic102 subunit of the human tfiiic transcription factor, were screened from ...200919521658
the epigenetic basis for centromere identity.the centromere serves as the control locus for chromosome segregation at mitosis and meiosis. in most eukaryotes, including mammals, the location of the centromere is epigenetically defined. the contribution of both genetic and epigenetic determinants to centromere function is the subject of current investigation in diverse eukaryotes. here we highlight key findings from several organisms that have shaped the current view of centromeres, with special attention to experiments that have elucidated ...200919521810
over expression and analysis of o-glycosylated recombinant human granulocyte colony stimulating factor in pichia pastoris using agilent 2100 bioanalyzer.recombinant human granulocyte colony stimulating factor (rhgcsf) was expressed in methylotrophic yeast pichia pastoris under the control of aox1 promoter after integration of the gcsf gene into p. pastoris genome. methanol induction of the pichia integrants yielded only 2mgl(-1) of rhgcsf whereas inclusion of surfactants during induction enhanced the yields to the level of 200-250mgl(-1) in shake flask studies after 72h of induction. preliminary studies in a bioreactor showed rhgcsf expression l ...200919527756
a robust correlation estimator and nonlinear recurrent model to infer genetic interactions in saccharomyces cerevisiae and pathways of pulmonary disease in homo sapiens.in order to identify genes involved in complex diseases, it is crucial to study the genetic interactions at the systems biology level. by utilizing modern high throughput microarray technology, it has become feasible to obtain gene expressions data and turn it into knowledge that explains the regulatory behavior of genes. in this study, an unsupervised nonlinear model was proposed to infer gene regulatory networks on a genome-wide scale. the proposed model consists of two components, a robust co ...200919527770
rep1p negatively regulating mdr1 efflux pump involved in drug resistance in candida albicans.overexpression of mdr1 efflux pump is a major mechanism contributing to drug resistance in candida albicans, the most common human fungal pathogen. to elucidate the regulatory pathway of drug resistance, we have identified a negative regulator of mdr1 and named it regulator of efflux pump 1 (rep1). overexpression of rep1 in saccharomyces cerevisiae increased susceptibility to fluconazole. furthermore, null mutations on rep1 decreased the susceptibility to antifungal drugs in c. albicans resultin ...200919527793
autonomous and 3d real-time multi-beam manipulation in a microfluidic environment.the generalized phase contrast (gpc) method of optical 3d manipulation has previously been used for controlled spatial manipulation of live biological specimen in real-time. these biological experiments were carried out over a time-span of several hours while an operator intermittently optimized the optical system. here we present gpc-based optical micromanipulation in a microfluidic system where trapping experiments are computer-automated and thereby capable of running with only limited supervi ...200619529649
relative contributions of cystathionine beta-synthase and gamma-cystathionase to h2s biogenesis via alternative trans-sulfuration reactions.in mammals, the two enzymes in the trans-sulfuration pathway, cystathionine beta-synthase (cbs) and cystathionine gamma-lyase (cse), are believed to be chiefly responsible for hydrogen sulfide (h2s) biogenesis. in this study, we report a detailed kinetic analysis of the human and yeast cbs-catalyzed reactions that result in h2s generation. cbs from both organisms shows a marked preference for h2s generation by beta-replacement of cysteine by homocysteine. the alternative h2s-generating reactions ...200919531479
fine-structured multi-scaling long-range correlations in completely sequenced genomes--features, origin, and classification.the sequential organization of genomes, i.e. the relations between distant base pairs and regions within sequences, and its connection to the three-dimensional organization of genomes is still a largely unresolved problem. long-range power-law correlations were found using correlation analysis on almost the entire observable scale of 132 completely sequenced chromosomes of 0.5 x 10(6) to 3.0 x 10(7) bp from archaea, bacteria, arabidopsis thaliana, saccharomyces cerevisiae, schizosaccharomyces po ...200919533117
fusion loop peptide of the west nile virus envelope protein is essential for pathogenesis and is recognized by a therapeutic cross-reactive human monoclonal antibody.west nile virus is an emerging pathogen that can cause fatal neurological disease. a recombinant human mab, mab11, has been described as a candidate for the prevention and treatment of west nile disease. using a yeast surface display epitope mapping assay and neutralization escape mutant, we show that mab11 recognizes the fusion loop, at the distal end of domain ii of the west nile virus envelope protein. ab mab11 cross-reacts with all four dengue viruses and provides protection against dengue ( ...200919535627
novel partners of spag11b isoform d in the human male reproductive tract.human sperm-associated antigen 11 (spag11) is closely related to beta-defensins in structure, expression, and function. like the beta-defensins, spag11 proteins are predominantly expressed in the male reproductive tract, where their best-known major roles are in innate host defense and reproduction. although several hypotheses have emerged to describe the evolution of beta-defensin and spag11 multifunctionality, few describe these multiple functions in terms of defensin interactions with specifi ...200919535787
regulation of autophagy by a beclin 1-targeted microrna, mir-30a, in cancer cells.beclin 1, the mammalian homologue of the yeast atg6, is a key autophagy-promoting gene that plays a critical role in the regulation of cell death and survival of various types of cells. however, recent studies have observed that the expression of beclin 1 is altered in certain diseases including cancers. the causes underlying the aberrant expression of beclin 1 remain largely unknown. we report here that micrornas (mirnas), a class of endogenous, 22-24 nucleotide noncoding rna molecules able to ...200919535919
amiodarone inhibits multiple drug resistance in yeast saccharomyces cerevisiae.amiodarone is a widely used antiarrhythmic drug. there is also evidence that amiodarone decreases multidrug resistance in human cell lines. in this paper, we have shown that amiodarone has similar effect on yeast, saccharomyces cerevisiae, decreasing multiple drug resistance. amiodarone stimulates the accumulation of ethidium bromide by inhibiting its efflux from the cells. the effect of amiodarone is much stronger on wild-type cells compared to the mutant with inactivated abc-transporters. inte ...200919536523
bioprocessing of wheat bran improves in vitro bioaccessibility and colonic metabolism of phenolic compounds.ferulic acid (fa) is the most abundant phenolic compound in wheat grain, mainly located in the bran. however, its bioaccessibility from the bran matrix is extremely low. different bioprocessing techniques involving fermentation or enzymatic and fermentation treatments of wheat bran were developed aiming at improving the bioaccessibility of phenolic compounds in bran-containing breads. the bioaccessibility of ferulic acid, p-coumaric acid, and sinapic acid was assessed with an in vitro model of u ...200919537710
a graph model based study on regulatory impacts of transcription factors of drosophila melanogaster and comparison across species.transcription factor binding sites and the cis-regulatory modules they compose are central determinants of gene regulation. the gene regulations in some model species have been well addressed. however, not as much is known about the fly due to the lack of experimental data. to study the transcription regulation of drosophila melanogaster genes, we analyzed the regulation data from chip chip experiments as well as the regulatory database. a graph-based approach is applied to study the impacts of ...200919538943
identification of a second independent binding site for the pcaf acetyltransferase in adenovirus e1a.the conserved region 3 (cr3) portion of the human adenovirus (hadv) 5 e1a protein functions as a potent transcriptional activator that induces expression of viral early genes during infection. expression of hadv-5 cr3 in the yeast saccharomyces cerevisiae inhibits growth, as do the corresponding regions of the hadv-3, 4, 9, 12 and 40 e1a proteins, which represent the remaining five hadv subgroups. growth inhibition is alleviated by disruption of the saga transcriptional regulatory complex, sugge ...200919541337
hidden killers: persistence of opportunistic fungal pathogens in the human host.opportunistic fungal pathogens are responsible for life-threatening systemic infections in immunocompromized individuals. yet, they are also able to persist in immunocompetent individuals through different strategies. this review explores recent advances in our understanding of several survival strategies: the establishment of a commensal relationship between yeast of the genus candida and the host; the formation of biofilms that allow microbes in these communities to be protected from chemical ...200919541532
the trypanosoma brucei sphingolipid synthase, an essential enzyme and drug target.sphingolipids are important components of eukaryotic membranes, particularly the plasma membrane, and are involved in a diverse array of signal transduction processes. in the eukaryota the biosynthetic pathway for the formation of these lipid species is largely conserved. however, in contrast to mammals which produce sphingomyelin (sm), several pathogenic fungi and protozoa synthesize inositol phosphorylceramide (ipc) as the primary phosphosphingolipid. this process is catalyzed by the enzyme ip ...200919545591
epigenetics of human t cells during the g0-->g1 transition.we investigated functional epigenetic changes that occur in primary human t lymphocytes during entry into the cell cycle and mapped these at the single-nucleosome level by chip-chip on tiling arrays for chromosomes 1 and 6. we show that nucleosome loss and flanking active histone marks define active transcriptional start sites (tsss). moreover, these signatures are already set at many inducible genes in quiescent cells prior to cell stimulation. in contrast, there is a dearth of the inactive his ...200919546172
soluble cytoplasmic expression, rapid purification, and characterization of cyanovirin-n as a his-sumo fusion.cyanovirin-n (cvn) is a promising antiviral candidate that has an extremely low sequence homology with any other known proteins. the efficient and soluble expression of biologically functional recombinant cvn (rcvn) is still an obstacle due to insufficient yield, aggregation, and abnormal modification. here, we describe an improved approach to preparing native rcvn from escherichia coli more efficiently. a fusion gene consisting of cvn and sumo (small ubiquitin-related modifier) and a hexahistid ...201019547966
audiometric and vestibular features in a second dutch dfna20/26 family with a novel mutation in actg1.we analyzed the phenotype in a 5-generation dfna20/26 family with a novel missense mutation in the actg1 gene (c.151g>a) and compared the findings to previous reports on dfna20/26 families.200919548389
nos1ap regulates dendrite patterning of hippocampal neurons through a carboxypeptidase e-mediated pathway.during neuronal development, neurons form elaborate dendritic arbors that receive signals from axons. additional studies are needed to elucidate the factors regulating the establishment of dendritic patterns. our work explored possible roles played by nitric oxide synthase 1 adaptor protein (nos1ap; also known as c-terminal pdz ligand of neuronal nitric oxide synthase or capon) in dendritic patterning of cultured hippocampal neurons. here we report that the long isoform of nos1ap (nos1ap-l) play ...200919553464
golph3 modulates mtor signalling and rapamycin sensitivity in cancer.genome-wide copy number analyses of human cancers identified a frequent 5p13 amplification in several solid tumour types, including lung (56%), ovarian (38%), breast (32%), prostate (37%) and melanoma (32%). here, using integrative analysis of a genomic profile of the region, we identify a golgi protein, golph3, as a candidate targeted for amplification. gain- and loss-of-function studies in vitro and in vivo validated golph3 as a potent oncogene. physically, golph3 localizes to the trans-golgi ...200919553991
high-level expression of a phage display-derived scfv in pichia pastoris.numerous techniques are available for investigating protein-ligand interactions. the phage display technique is one such method routinely used to identify antibody-antigen interactions and has the benefit of being easily adaptable to high-throughput screening platforms. once identified, antigen-binding domains on fragment antibodies or single-chain fragment antibodies (scfv) can be expressed and purified for further studies. in this chapter, we describe a method for high-level expression of a ph ...200919554300
grp94, the endoplasmic reticulum hsp90, has a similar solution conformation to cytosolic hsp90 in the absence of nucleotide.the molecular chaperone, hsp90, is an essential eukaryotic protein that assists in the maturation and activation of client proteins. hsp90 function depends upon the binding and hydrolysis of atp, which causes large conformational rearrangements in the chaperone. hsp90 is highly conserved from bacteria to eukaryotes, and similar nucleotide-dependent conformations have been demonstrated for the bacterial, yeast, and human proteins. there are, however, important species-specific differences in the ...200919554567
functional conservation of trnase zl among saccharomyces cerevisiae, schizosaccharomyces pombe and humans.although trnase z from various organisms was shown to process nuclear trna 3' ends in vitro, only a very limited number of studies have reported its in vivo biological functions. trnase z is present in a short form, trnase z(s), and a long form, trnase z(l). unlike saccharomyces cerevisiae, which contains one trnase z(l) gene (sctrz1) and humans, which contain one trnase z(l) encoded by the prostate-cancer susceptibility gene elac2 and one trnase z(s), schizosaccharomyces pombe contains two trna ...200919555350
roles of proteasomal 19s regulatory particles in promoter loading of thyroid hormone receptor.19s regulatory particles (19srp) of 26s proteasome participate in multiple steps of gene transcription in yeast. we previously showed that tat-binding protein-1 (tbp-1), an atpase of 19srp, interacts with thyroid hormone receptor (tr) and enhances tr-mediated transcription synergistically with steroid receptor coactivator-1 (src-1). to further elucidate the roles of atpases and a non-atpase component of 19srp in gene regulation by tr, we investigated whether knockdown (ko) of tbp-1, trip1 or rpn ...200919555666
to be or not to be demethylated. 200919556875
analysis of dram-related proteins reveals evolutionarily conserved and divergent roles in the control of autophagy.autophagy is a membrane-trafficking process that serves to deliver cytoplasmic proteins and organelles to the lysosome for degradation. the process is genetically defined and many of the factors involved are conserved from yeast to man. recently, a number of new autophagy regulators have been defined, including the damage-regulated autophagy modulator (dram), which is a lysosomal protein that links autophagy and the tumor suppressor, p53. we describe here analysis of dram-related proteins which ...200919556885
the adaptor protein lad/tsad mediates laminin-dependent t cell migration via association with the 67 kda laminin binding protein.the adaptor protein, lad/tsad, plays essential roles in t cell activation. to further understand the functions of this protein, we performed yeast two-hybrid screening using tsad as bait and identified 67 kda laminin binding protein (lbp) as the interacting partner. subsequently, tsad-lbp interaction was confirmed in d1.1 t cell line. upon costimulation by t cell receptor (tcr) plus laminin crosslinking or tcr plus integrin alpha6 crosslinking, lbp was coimmunoprecipitated with tsad. moreover, t ...200919561400
effect of yeast-derived beta-glucan in conjunction with bevacizumab for the treatment of human lung adenocarcinoma in subcutaneous and orthotopic xenograft models.human lung cancer is the leading cause of cancer death worldwide. bevacizumab, a monoclonal antibody against vascular endothelial growth factor (vegf), in combination with chemotherapy showed significant therapeutic efficacy in human lung cancer patients. however, increased adverse effects limit its clinical utilization. previous studies demonstrated that polysaccharide beta-glucan significantly augments antitumor monoclonal antibody-mediated efficacy via stimulation of the innate effector neutr ...200919561538
antimicrobial activity of hymenaea martiana towards dermatophytes and cryptococcus neoformans.the biological activity of crude extract and fractions of hymenaea martiana was evaluated against a panel of human pathogenic fungi. the crude extracts and hydroalcoholic fractions (e) showed a high activity against cryptococcus neoformans species complex isolates with mics between 2 and 64 μg ml(-1). the methanolic (c) and butanolic (d) fractions were the most active against trichopyton rubrum, trichopyton mentagrophytes and microsporum canis with mics between 8 and 256 μg ml(-1). none of the e ...201019563478
the mitochondrial protein translocation motor: structural conservation between the human and yeast tim14/pam18-tim16/pam16 co-chaperones.most of our knowledge regarding the process of protein import into mitochondria has come from research employing saccharomyces cerevisiae as a model system. recently, several mammalian homologues of the mitochondrial motor proteins were identified. of particular interest for us is the human tim14/pam18-tim16/pam16 complex. we chose a structural approach in order to examine the evolutionary conservation between yeast tim14/pam18-tim16/pam16 proteins and their human homologues. for this purpose, w ...200919564938
transcriptome adaptation of group b streptococcus to growth in human amniotic fluid.streptococcus agalactiae (group b streptococcus) is a bacterial pathogen that causes severe intrauterine infections leading to fetal morbidity and mortality. the pathogenesis of gbs infection in this environment is poorly understood, in part because we lack a detailed understanding of the adaptation of this pathogen to growth in amniotic fluid. to address this knowledge deficit, we characterized the transcriptome of gbs grown in human amniotic fluid (af) and compared it with the transcriptome in ...200919568429
17beta-hydroxysteroid dehydrogenase type 8 and carbonyl reductase type 4 assemble as a ketoacyl reductase of human mitochondrial fas.mitochondrial fatty acid synthesis (fas) generates the octanoyl-group that is required for the synthesis of lipoic acid and is linked to mitochondrial rna metabolism. all of the human enzymes involved in mitochondrial fas have been characterized except for beta-ketoacyl thioester reductase (hskar), which catalyzes the second step in the pathway. we report here the unexpected finding that a heterotetramer composed of human 17beta-hydroxysteroid dehydrogenase type 8 (hs17beta-hsd8) and human carbo ...200919571038
characterization of the aspergillus fumigatus phosphomannose isomerase pmi1 and its impact on cell wall synthesis and morphogenesis.phosphomannose isomerase (pmi) is an enzyme catalysing the interconversion of mannose 6-phosphate (man-6-p) and fructose 6-phosphate (fru-6-p). the reaction catalysed by pmi is the first committed step in the synthesis of mannose-containing sugar chains and provides a link between glucose metabolism and mannosylation. in this study, the pmi1 gene was identified to encode pmi in the human fungal pathogen aspergillus fumigatus. characterization of a. fumigatus pmi1 expressed in escherichia coli re ...200919574302
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