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Cell. 1999 Apr 30;97(3):349-60.

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

Author information

1
Biochemistry, Wyeth Research, Cambridge, Massachusetts 02140, USA. adessen@genetics.com

Abstract

Cytosolic phospholipase A2 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 cPLA2 at 2.5 A. cPLA2 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.

PMID:
10319815
DOI:
10.1016/s0092-8674(00)80744-8
[Indexed for MEDLINE]
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