Document Detail

The molecular basis of phosphatidylcholine preference of human group-V phospholipase A2.
MedLine Citation:
PMID:  10839997     Owner:  NLM     Status:  MEDLINE    
Human group-V phospholipase A(2) (hVPLA(2)) is a secretory phospholipase A(2) (PLA(2)) that is involved in eicosanoid formation in such inflammatory cells as macrophages and mast cells. We showed that hVPLA(2) can bind phosphatidylcholine membranes and hydrolyse phosphatidylcholine molecules much more efficiently than human group-IIa PLA(2), which accounts for its high activity on the outer plasma membrane of mammalian cells. To understand the molecular basis of the high phosphatidylcholine specificity of hVPLA(2), we mutated several residues (Gly-53, Glu-56 and Glu-57) that might be involved in interaction with an active-site-bound phospholipid molecule. Phospholipid head-group specificities of mutants determined using polymerized mixed-liposome substrates indicate that a small glycine residue in position 53 is important for accommodating a bulky choline head group. Also, results indicated that two anionic residues, Glu-56 and Glu-57, favourably interact with cationic head groups of phosphatidylcholine and phosphatidylethanolamine. Together, these steric and electrostatic properties of the active site of hVPLA(2) allow for effective binding and hydrolysis of a bulky cationic choline head group of phosphatidylcholine, which is unique among mammalian secretory PLA(2)s.
K P Kim; S K Han; M Hong; W Cho
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Biochemical journal     Volume:  348 Pt 3     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-08-03     Completed Date:  2000-08-03     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  643-7     Citation Subset:  IM    
Department of Chemistry (M/C 111), University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607-7061, USA.
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MeSH Terms
Amino Acid Sequence
Models, Molecular
Phosphatidylcholines / metabolism*
Phospholipases A / chemistry,  genetics,  metabolism*
Phospholipases A2
Protein Conformation
Sequence Homology, Amino Acid
Substrate Specificity
Grant Support
Reg. No./Substance:
0/Phosphatidylcholines; EC 3.1.1.-/Phospholipases A; EC A2

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