Asp49 phospholipase A2-elaidoylamide complex:: a new mode of inhibition

被引：16

作者：

Georgieva, DN

Rypniewski, W

Gabdoulkhakov, A

Genov, N

Betzel, C

机构：

[1] Univ Hamburg, Klinikum Eppendorf, Inst Biochem & Mol Biol 1, Zentrum Expt Med,DESY, D-22603 Hamburg, Germany

[2] Bulgarian Acad Sci, Inst Organ Chem, BU-1113 Sofia, Bulgaria

[3] RAS, Inst Prot Res, Pushchino 142290, Moscow Region, Russia

[4] Polish Acad Sci, Inst Bioorgan Chem, PL-61704 Poznan, Poland

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2004年 / 319卷 / 04期

关键词：

phospholipase A(2); neurotoxin; elaidoylamide; X-ray structure;

D O I：

10.1016/j.bbrc.2004.05.106

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The inhibition of phospholipase A(2)s (PLA(2)s) is of pharmacological and therapeutic interest because these enzymes are involved in several inflammatory diseases. Elaidoylamide is a powerful inhibitor of a neurotoxic PLA(2) from the Vipera ammodytes merid-ionalis venom. The X-ray structure of the enzyme-inhibitor complex reveals a new mode of Asp49 PLA(2) inhibition by a fatty acid hydrocarbon chain. The structure contains two identical homodimers in the asymmetric unit. In each dimer one subunit is rotated by 180 with respect to the other and the two molecules are oriented head-to-tail. One molecule of elaidoylamide is bound simultaneously to the substrate binding sites of two associated neurotoxic phospholipase A(2) molecules. The inhibitor binds symmetrically to the hydrophobic channels of the two monomers. The structure can be used to design anti-inflammatory drugs. (C) 2004 Elsevier Inc. All rights reserved.

引用

页码：1314 / 1321

页数：8

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