Document Detail


The Interaction of Human Synovial Phospholipase A2 with Mixed Lipid Bilayers: A Coarse-Grain and All-Atom Molecular Dynamics Simulation Study.
MedLine Citation:
PMID:  23343574     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Human secreted phospholipase A2s have been shown to promote inflammation in mammals by catalyzing the first step of the arachidonic acid pathway by breaking down phospholipids, producing fatty acids including arachidonic acid. They bind to the membrane water interface to access their phospholipid substrates from the membrane. Their binding modes on membrane surfaces are regulated by diverse factors, including the membrane charge, fluidity and heterogeneity. Influences of these factors on the binding modes of the enzymes are not well understood up to now. Here we have studied several human synovial phospholipase A2 (hs-PLA2)/mixed-bilayer systems through a combined coarse-grain and all-atom molecular dynamics simulations. It was found that hydrophobic residues LEU2, VAL3, ALA18, LEU19, PHE23, GLY30, PHE63 that form the edge of the entrance of the hydrophobic binding pocket in hs-PLA2 tend to penetrate into the hydrophobic area of lipid bilayers, and more than half of the total amino residues contact with the lipid head groups. Each enzyme molecule forms 19~38 hydrogen bonds with the bilayer it binds to, most of which are with the phosphate groups. Analysis of root mean square deviation (RMSD) shows that residue VAL30~THR40, TYR66~GLN80, and 107LYS~118ARG have relatively large RMSD during all-atom molecular dynamics simulations, in accordance with the observation of enlarged entrance region of the hydrophobic binding pocket. The amino acid sequences forming the entrance of the binding pocket prefer to interact with lipid molecules that are more fluid or negatively charged, and the opening of the binding pocket would be larger when the lipid components possess higher fluidity.
Authors:
Shan-Shan Qin; Yang-Xin Yu; Qi-Kai Li; Zhi-Wu Yu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-24
Journal Detail:
Title:  Biochemistry     Volume:  -     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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