Document Detail


Identification of key residues responsible for enzymatic and platelet-aggregation-inhibiting activities of acidic phospholipase A2S from Agkistrodon halys Pallas.
MedLine Citation:
PMID:  11288728     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Site-directed mutagenesis was used to probe the structural and functional relationship of acidic phospholipase A2 from Agkistrodon halys Pallas. The mutants are AP-E6R (E6R), AP-D115K (D115K), AP-6R115K (E6R, D115K), AP-Y118M (Y118M), and AP-W119T (W119T). All mutants were inserted into a bacterial expression vector and effectively expressed in E. coli RR1. The purified recombinant enzymes were used to assay for enzymatic and inhibiting platelet aggregation activities. The enzymatic activities of AP-D115K, AP-Y118M and AP-W119T are close to that of denatured-refolded acidic phospholipase A2, while the enzymatic activities of AP-E6R, AP-6R1 15K are lower than that of denatured-refolded acidic phospholipase A2 (AP-WT). In these five mutants, AP-Y118M showed strongest inhibiting effect on platelet aggregation, which is the same as that of AP-WT, AP-W119T showed only modest activity and AP-E6R, AP-D115K, AP-6R115K showed little activity. To study the structural and functional relationships among these five mutants, molecular modeling of these five mutants was done. The roles of various amino acid residues in the enzymatic activity and pharmacological activity of acidic phospholipase A2 are discussed.
Authors:
X Liu; X Wu; Y Zhou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of natural toxins     Volume:  10     ISSN:  1058-8108     ISO Abbreviation:  J Nat Toxins     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-04-05     Completed Date:  2001-05-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9208016     Medline TA:  J Nat Toxins     Country:  United States    
Other Details:
Languages:  eng     Pagination:  43-55     Citation Subset:  IM    
Affiliation:
Shanghai Institute of Biochemistry, The Chinese Academy of Science.
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MeSH Terms
Descriptor/Qualifier:
Adult
Amino Acid Sequence
Amino Acid Substitution
Animals
Crotalid Venoms / genetics,  pharmacology*
Escherichia coli / enzymology
Genetic Vectors
Humans
Models, Molecular
Molecular Sequence Data
Mutagenesis, Site-Directed
Phospholipases A / genetics,  pharmacology*
Phospholipases A2
Platelet Aggregation / drug effects*
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Crotalid Venoms; EC 3.1.1.-/Agkistrodon platelet aggregation inhibitor; EC 3.1.1.-/Phospholipases A; EC 3.1.1.4/Phospholipases A2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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