| non-steroidal anti-inflammatory drugs as potent inhibitors of phospholipase a2: structure of the complex of phospholipase a2 with niflumic acid at 2.5 angstroms resolution. | phospholipase a(2) (pla(2); ec 3.1.3.4) catalyzes the first step of the production of proinflammatory compounds collectively known as eicosanoids. the binding of phospholipid substrates to pla(2) occurs through a well formed hydrophobic channel. surface plasmon resonance studies have shown that niflumic acid binds to naja naja sagittifera pla(2) with an affinity that corresponds to a dissociation constant (k(d)) of 4.3 x 10(-5) m. binding studies of pla(2) with niflumic acid were also carried ou ... | 2005 | 16301791 |
| crystal structure of the complex of group i pla2 with a group ii-specific peptide leu-ala-ile-tyr-ser (laiys) at 2.6 a resolution. | phospholipases a(2)s (pla(2)s) are widely distributed in mammals and snake venoms. they catalyze the production of arachidonic acid from membrane phospholipids leading to the bioynthesis of pro-inflammatory eicosanoids. a peptide leu-ala-ile-tyr-ser (laiys) was designed and synthesized as a specific inhibitor of pla(2). it was shown earlier that the peptide bound to group ii pla(2) specifically and had a dissociation constant (k(d)) of 8.8 x 10(-9) m. in the present studies for the binding of la ... | 2005 | 16278156 |
| protein interactions between the c-terminus of aβ-peptide and phospholipase a2--a structure biology based approach to identify novel alzheimer's therapeutics. | amyloid β (aβ) polypeptide plays a key role in determining the state of protein aggregation in alzheimer's disease. the hydrophobic c-terminal part of the aβ peptide is critical in triggering the transformation from α-helical to β- sheet structure. we hypothesized that phospholipase a2 (pla2) may inhibit the aggregation of aβ peptide by interacting with the peptide and keeping the two peptide chains apart. in order to examine the nature of interactions between pla2 and aβ peptide, we prepared an ... | 2014 | 25230229 |
| structure of n-terminal sequence asp-ala-glu-phe-arg-his-asp-ser of aβ-peptide with phospholipase a2 from venom of andaman cobra sub-species naja naja sagittifera at 2.0 å resolution. | alzheimer's disease (ad) is one of the most significant social and health burdens of the present century. plaques formed by extracellular deposits of amyloid β (aβ) are the prime player of ad's neuropathology. studies have implicated the varied role of phospholipase a2 (pla2) in brain where it contributes to neuronal growth and inflammatory response. overall contour and chemical nature of the substrate-binding channel in the low molecular weight pla2s are similar. this study involves the reducti ... | 2014 | 24619194 |
| crystal structure of a heterodimer of phospholipase a2 from naja naja sagittifera at 2.3 a resolution reveals the presence of a new pla2-like protein with a novel cys 32-cys 49 disulphide bridge with a bound sugar at the substrate-binding site. | the crystal structure of the phospholipase a2 (pla2) heterodimer from naja naja sagittifera reveals the presence of a new pla2-like protein with eight disulphide bridges. the heterodimer is formed between a commonly observed group i pla2 having seven characteristic disulfide bonds and a novel pla2-like protein (cys-pla2) containing two extra cysteines at two highly conserved sites (positions 32 and 49) of structural and functional importance. the crystals of the heterodimer belong to tetragonal ... | 2006 | 16287060 |
| crystal structure of a novel phospholipase a2 from naja naja sagittifera with a strong anticoagulant activity. | this is the first pla(2) crystal structure from group i that shows a strong anticoagulant property. the monomeric pla(2) was purified from the venom of naja naja sagittifera (indian cobra). its amino acid sequence has been determined using cdna technique. the amino acid sequence of spla(2) contains three positively charged and two negatively charged residues in the segment 54-71 (numbering scheme of spla(2)) thus giving this region an overall cationic amphiphilic surface. this suggested the pres ... | 2005 | 16269164 |
| crystal structure of a novel phospholipase a2 from crude venom of indian cobra sub-species naja naja sagittifera at 1.48 angstoms resolution. | secretory phospholipase a2s (pla2s), the structurally-homologous enzymes share a common qualitative catalytic site, but differ greatly in their pharmacological properties and toxicities. there has been a recognizable pattern of mutations in the primary sequence of pla2s that alter their catalytic properties significantly. in the present study, the amino acid sequence and the three-dimensional structure of a new isoform of pla2 from crude venom of indian cobra sub-species naja naja sagittifera (n ... | 2005 | 23923535 |
| structure of the zinc-induced heterodimer of two calcium-free isoforms of phospholipase a2 from naja naja sagittifera at 2.7 angstroms resolution. | the crystal structure of a zinc-induced heterodimer of two metal-free isoforms of a cobra venom phospholipase a(2) has been determined at 2.7 angstroms resolution. the crystals belong to space group p4(1), with unit-cell parameters a = b = 65.5, c = 58.4 angstroms, and have a single dimer in the asymmetric unit. the structure has been refined to r(cryst) and r(free) factors of 0.188 and 0.232, respectively. the two isoforms have a sequence identity of 82%. the zinc ion forms a fivefold coordinat ... | 2005 | 15735340 |
| design of specific peptide inhibitors for group i phospholipase a2: structure of a complex formed between phospholipase a2 from naja naja sagittifera (group i) and a designed peptide inhibitor val-ala-phe-arg-ser (vafrs) at 1.9 a resolution reveals unique features. | phospholipase a(2) (pla(2)) (e. c. 3.1.1.4) is a common enzyme in the two-way cascade mechanism leading to the production of proinflammatory compounds known as eicosanoids. the binding of phospholipase a(2) to the membrane surface and hydrolysis of phospholipids are thought to involve the formation of a hydrophobic channel into which a single substrate molecule diffuses before its cleavage. to regulate the production of proinflammatory compounds, a specific peptide inhibitor val-ala-phe-arg-ser ... | 2003 | 14529280 |
| exploring the structural and functional aspects of the phospholipase a2 from naja spp. | naja spp. venom is a natural source of active compounds with therapeutic application potential. phospholipase a2 (pla2) is abundant in the venom of naja spp. and can perform neurotoxicity, cytotoxicity, cardiotoxicity, and hematological disorders. the pla2s from naja spp. venoms are asp 49 isoenzymes with the exception of pla2 cys 49 from naja sagittifera. when looking at the functional aspects, the neurotoxicity occurs by pla2 called β-toxins that have affinity for phosphatidylcholine in nerve ... | 2019 | 31421173 |