Linked Life Data

16552142

Source:http://linkedlifedata.com/resource/pubmed/id/16552142

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 4
pubmed:dateCreated
2006-3-22
pubmed:abstractText
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 (diclofenac) has been determined. The preformed complex was crystallized by equilibrating the protein solution against a mixture of 0.20 M ammonium sulfate and 30% PEG 4000. The crystals belong to space group P4(3), with unit-cell parameters a = b = 53.0, c = 48.4 A. The structure was solved by the molecular-replacement method and refined to R(cryst) and R(free) factors of 0.192 and 0.211, respectively, using reflections to 2.7 A resolution. The structure showed that diclofenac occupies a very favourable position in the centre of the substrate-binding hydrophobic channel that allows a number of intermolecular interactions. The binding mode of diclofenac involved crucial interactions with important residues for substrate recognition such as Asp49, His48 and Gly30. In addition, it included three new interactions involving its Cl atoms with Phe5, Ala18 and Tyr22. It also showed an extensive network of hydrophobic interactions involving almost all of the residues of the substrate-binding hydrophobic channel. The binding affinity of diclofenac was determined using surface plasmon resonance, which gave an equilibrium constant of 4.8 +/- 0.2 x 10(-8) M.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0907-4449
pubmed:author
pubmed:issnType
Print
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
410-6
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16552142-Animals, pubmed-meshheading:16552142-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:16552142-Binding Sites, pubmed-meshheading:16552142-Calcium, pubmed-meshheading:16552142-Catalysis, pubmed-meshheading:16552142-Crystallization, pubmed-meshheading:16552142-Crystallography, X-Ray, pubmed-meshheading:16552142-Diclofenac, pubmed-meshheading:16552142-Enzyme Inhibitors, pubmed-meshheading:16552142-Group II Phospholipases A2, pubmed-meshheading:16552142-Kinetics, pubmed-meshheading:16552142-Models, Molecular, pubmed-meshheading:16552142-Phospholipases A, pubmed-meshheading:16552142-Phospholipases A2, pubmed-meshheading:16552142-Protein Binding, pubmed-meshheading:16552142-Protein Structure, Tertiary, pubmed-meshheading:16552142-Russell's Viper, pubmed-meshheading:16552142-Static Electricity, pubmed-meshheading:16552142-Viper Venoms, pubmed-meshheading:16552142-Water
pubmed:year
2006
pubmed:articleTitle
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.
pubmed:affiliation
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't