| crystal structures of the complexes of a group iia phospholipase a2 with two natural anti-inflammatory agents, anisic acid, and atropine reveal a similar mode of binding. | secretory low molecular weight phospholipase a(2)s (pla(2)s) are believed to be involved in the release of arachidonic acid, a precursor for the biosynthesis of pro-inflammatory eicosanoids. therefore, the specific inhibitors of these enzymes may act as potent anti-inflammatory agents. similarly, the compounds with known anti-inflammatory properties should act as specific inhibitors. two plant compounds, (a) anisic acid (4-methoxy benzoic acid) and (b) atropine (8-methyl-8-azabicyclo oct-3-hydro ... | 2006 | 16596639 |
| three-dimensional structure of a presynaptic neurotoxic phospholipase a2 from daboia russelli pulchella at 2.4 a resolution. | the phospholipase a(2 )from daboia russelli pulchella (dpla(2)) is the only known member of subclass ii of group iia. the three-dimensional structure of this presynaptic neurotoxic dpla(2) enzyme has been determined at 2.4 a resolution. the structure was determined by the molecular replacement method using the model crotalus atrox, and refined using x-plor to a final r-factor of 18.8 % for all data in the resolution range 20.0 a-2.4 a. the final refined model comprises 1888 atoms from two crysta ... | 2000 | 10686108 |
| regulation of catalytic function by molecular association: structure of phospholipase a2 from daboia russelli pulchella (dpla2) at 1.9 a resolution. | the crystal structure of phospholipase a(2) from the venom of daboia russelli pulchella has been refined to an r factor of 0.216 using 17,922 reflections to 1.9 a resolution. the structure contains two crystallographically independent molecules in the asymmetric unit. the overall conformations of the two molecules are essentially the same except for three regions, namely the calcium-binding loop including trp31, the beta-wing and the c-terminal residues 119-131. although these differences have a ... | 2001 | 11717491 |
| purification, crystallization and preliminary x-ray crystallographic analysis of a phospholipase a2 from daboia russelli pulchella. | phospholipases are esterolytic enzymes which hydrolyze glycerophospholipids. the pharmacological efficiency of phospholipase a2 (pla2) enzymes is reflected by their specificity towards a tissue or organ. the russell's viper has been classified into two classes. class 1 contains viper russelli russelli, viper russelli siamensis and viper russelli formosensis, whereas class 2 contains daboia russelli pulchella. the sequence identity between the pla2s from these two classes is 47%. the novel pla2 f ... | 1999 | 10089336 |
| crystal structure of the complex of the secretory phospholipase a2 from daboia russelli pulchella with an endogenic indole derivative, 2-carbamoylmethyl-5-propyl-octahydro-indol-7-yl-acetic acid at 1.8 a resolution. | phospholipase a2 (pla2) enzymes from snake venoms are approximately 14 kda secretory proteins and catalyze the release of arachidonic acid which is the precursor of proinflammatory mediators such as prostaglandins, leukotrienes, thromboxanes and platelet-activating factors. the structure of the pla2 enzyme purified from the venom of daboia russelli pulchella was determined using molecular replacement method and refined to an r value of 18.3% for all the reflections to 1.8 a resolution. the struc ... | 2005 | 16122995 |
| simultaneous inhibition of anti-coagulation and inflammation: crystal structure of phospholipase a2 complexed with indomethacin at 1.4 a resolution reveals the presence of the new common ligand-binding site. | a novel ligand-binding site with functional implications has been identified in phospholipase a(2) (pla(2)). the binding of non-steroidal anti-inflammatory agent indomethacin at this site blocks both catalytic and anti-coagulant actions of pla(2). a group iia pla(2) has been isolated from daboia russelli pulchella (russell's viper) which is enzymatically active as well as induces a strong anti-coagulant action. the binding studies have shown that indomethacin reduces the effects of both anti-coa ... | 2013 | 19462410 |
| pyrazolo[3,4-d]pyrimidines as inhibitor of anti-coagulation and inflammation activities of phospholipase a 2 : insight from molecular docking studies. | phospholipase a2 (pla2), isolated from daboia russelli pulchella (russell's viper), is enzymatically active as well as induces several pharmacological disorders including neurotoxicity, myotoxicity, cardiotoxicity, anti-coagulant, hemolytic, and platelet effects. indomethacin reduces the effects of anti-coagulant and pro-inflammatory actions of pla2. pyrazolo[3,4-d]pyrimidines constitute a class of naturally occurring fused uracils that posses diverse biological activities. the in-silico docking ... | 2013 | 23860918 |
| structures and binding studies of the complexes of phospholipase a2 with five inhibitors. | phospholipase a2 (pla2) catalyzes the hydrolysis of phospholipids into arachidonic acid and lysophospholipids. arachidonic acid is used as a substrate in the next step of the multistep pathway leading to the production of eicosanoids. the eicosanoids, in extremely low concentrations, are required in a number of physiological processes. however, the increase in their concentrations above the essential physiological requirements leads to various inflammatory conditions. in order to prevent the unw ... | 2015 | 25541253 |
| molecular dynamics simulations reveal structural insights into inhibitor binding modes and functionality in human group iia phospholipase a2. | human group iia phospholipase a2(hgiia) promotes inflammation in immune-mediated pathologies by regulating the arachidonic acid pathway through both catalysis-dependent and -independent mechanisms. the hgiia crystal structure, both alone and inhibitor-bound, together with structures of closely related snake-venom-derived secreted phospholipase enzymes has been well described. however, differentiation of biological and nonbiological contacts and the relevance of structures determined from snake v ... | 2017 | 28056488 |
| design of specific peptide inhibitors of phospholipase a2: structure of a complex formed between russell's viper phospholipase a2 and a designed peptide leu-ala-ile-tyr-ser (laiys). | phospholipase a(2) (ec 3.1.1.4) is a key enzyme of the cascade mechanism involved in the production of proinflammatory compounds known as eicosanoids. the binding of phospholipase a(2) to membrane surfaces and the hydrolysis of phospholipids are thought to involve the formation of a hydrophobic channel into which a single substrate molecule diffuses before cleavage. in order to regulate the production of proinflammatory compounds, a specific peptide inhibitor of pla(2), leu-ala-ile-tyr-ser, has ... | 2002 | 12351825 |
| antibacterial potential of a basic phospholipase a2 (vrv-pl-v) of daboia russellii pulchella (russell's viper) venom. | microbial/bacterial resistance against antibiotics is considered as a potentially serious threat to public health. further, as these antibiotics elicit side effects, there is interest in developing new molecules with novel modes of action from diverse organisms. along these lines, in this study the antibacterial potential of the basic protein vrv-pl-v (vipera russellii venom phospholipase a2 fraction v) of daboia russellii pulchella venom was evaluated. vrv-pl-v demonstrated a potent antibacteri ... | 2014 | 25540009 |
| 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 |
| specific binding of non-steroidal anti-inflammatory drugs (nsaids) to phospholipase a2: structure of the complex formed between phospholipase a2 and diclofenac at 2.7 a resolution. | type iia secretory phospholipase a2 (pla2) enzymes catalyze the hydrolysis of the sn-2 ester bond of glycerophospholipids to release fatty acids and lysophospholipids. in order to elucidate the role of pla2 in inflammatory disorders and to determine the mode of binding of non-steroidal anti-inflammatory drugs (nsaids) to pla2, the detailed three-dimensional structure of a complex formed between a group iia pla2 from daboia russelli pulchella and 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid (d ... | 2006 | 16552142 |
| virtual analysis of structurally diverse synthetic analogs as inhibitors of snake venom secretory phospholipase a2. | due to the toxic pathophysiological role of snake venom phospholipase a2 (pla2 ), its compelling limitations to anti-venom therapy in humans and the need for alternative therapy foster considerable pharmacological interest towards search of pla2 specific inhibitors. in this study, an integrated approach involving homology modeling, molecular dynamics and molecular docking studies on vrv-pl-v (vipera russellii venom phospholipase a2 fraction-v) belonging to group ii-b secretory pla2 from daboia r ... | 2016 | 26218369 |