Crystal structure of human cytosolic phospholipase A2 reveals a novel topology and catalytic mechanism

被引：306

作者：

Dessen, A ^{[1
]}

Tang, J ^{[1
]}

Schmidt, H ^{[1
]}

Stahl, M ^{[1
]}

Clark, JD ^{[1
]}

Seehra, J ^{[1
]}

Somers, WS ^{[1
]}

机构：

[1] Wyeth Ayerst Res, Biochem, Cambridge, MA 02140 USA

来源：

CELL | 1999年 / 97卷 / 03期

关键词：

D O I：

10.1016/S0092-8674(00)80744-8

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：

Cytosolic phospholipase A, initiates the biosynthesis of prostaglandins, leukotrienes, and platelet-activating factor (PAF), mediators of the pathophysiology of asthma and arthritis. Here, we report the X-ray crystal structure of human cPLA(2) at 2.5 Angstrom. cPLA(2) consists of an N-terminal calcium-dependent lipid-binding/C2 domain and a catalytic unit whose topology is distinct from that of other lipases. An unusual Ser-Asp dyad located in a deep cleft at the center of a predominantly hydrophobic funnel selectively cleaves arachidonyl phospholipids. The structure reveals a flexible lid that must move to allow substrate access to the active site, thus explaining the interfacial activation of this important lipase.

引用

页码：349 / 360

页数：12

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