PMID- 10319815
OWN - NLM
STAT- MEDLINE
DCOM- 19990520
LR  - 20190705
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 97
IP  - 3
DP  - 1999 Apr 30
TI  - Crystal structure of human cytosolic phospholipase A2 reveals a novel topology
      and catalytic mechanism.
PG  - 349-60
AB  - 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.
FAU - Dessen, A
AU  - Dessen A
AD  - Biochemistry, Wyeth Research, Cambridge, Massachusetts 02140, USA.
      adessen@genetics.com
FAU - Tang, J
AU  - Tang J
FAU - Schmidt, H
AU  - Schmidt H
FAU - Stahl, M
AU  - Stahl M
FAU - Clark, J D
AU  - Clark JD
FAU - Seehra, J
AU  - Seehra J
FAU - Somers, W S
AU  - Somers WS
LA  - eng
SI  - PDB/1CJY
PT  - Journal Article
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Phospholipids)
RN  - 0 (Solvents)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - EC 3.- (Hydrolases)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Arachidonic Acid/metabolism
MH  - Binding Sites/*genetics
MH  - CHO Cells
MH  - Calcium/*metabolism
MH  - Catalytic Domain/*genetics
MH  - Cricetinae
MH  - Crystallography, X-Ray
MH  - Cytosol/enzymology
MH  - Humans
MH  - Hydrolases/chemistry/metabolism
MH  - Molecular Sequence Data
MH  - Phospholipases A/*chemistry/genetics/*metabolism
MH  - Phospholipases A2
MH  - Phospholipids/metabolism
MH  - Protein Folding
MH  - Protein Structure, Secondary
MH  - Protein Structure, Tertiary
MH  - Sequence Homology, Amino Acid
MH  - Solvents
EDAT- 1999/05/13 00:00
MHDA- 1999/05/13 00:01
CRDT- 1999/05/13 00:00
PHST- 1999/05/13 00:00 [pubmed]
PHST- 1999/05/13 00:01 [medline]
PHST- 1999/05/13 00:00 [entrez]
AID - S0092-8674(00)80744-8 [pii]
AID - 10.1016/s0092-8674(00)80744-8 [doi]
PST - ppublish
SO  - Cell. 1999 Apr 30;97(3):349-60. doi: 10.1016/s0092-8674(00)80744-8.