Linked Life Data

10931177

Source:http://linkedlifedata.com/resource/pubmed/id/10931177

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2000-10-18
pubmed:abstractText
Human secreted group IIA phospholipase A2 (hGIIA) was reported to inhibit prothrombinase activity because of binding to factor Xa. This study further shows that hGIIA and its catalytically inactive H48Q mutant prolong the lag time of thrombin generation in human platelet-rich plasma with similar efficiency, indicating that hGIIA exerts an anticoagulant effect independently of phospholipid hydrolysis under ex vivo conditions. Charge reversal of basic residues on the interfacial binding surface (IBS) of hGIIA leads to decreased ability to inhibit prothrombinase activity, which correlates with a reduced affinity for factor Xa, as determined by surface plasmon resonance. Mutation of other surface-exposed basic residues, hydrophobic residues on the IBS, and His48, does not affect the ability of hGIIA to inhibit prothrombinase activity and bind to factor Xa. Other basic, but not neutral or acidic, mammalian secreted phospholipases A2 (sPLA2s) exert a phospholipid-independent inhibitory effect on prothrombinase activity, suggesting that these basic sPLA2s also bind to factor Xa. In conclusion, this study demonstrates that the anticoagulant effect of hGIIA is independent of phospholipid hydrolysis and is based on its interaction with factor Xa, leading to prothrombinase inhibition, even under ex vivo conditions. This study also shows that such an interaction involves basic residues located on the IBS of hGIIA, and suggests that other basic mammalian sPLA2s may also inhibit blood coagulation by a similar mechanism to that described for hGIIA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:volume
267
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4960-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10931177-Amino Acid Sequence, pubmed-meshheading:10931177-Amino Acid Substitution, pubmed-meshheading:10931177-Animals, pubmed-meshheading:10931177-Base Sequence, pubmed-meshheading:10931177-Bothrops, pubmed-meshheading:10931177-Factor Xa, pubmed-meshheading:10931177-Group II Phospholipases A2, pubmed-meshheading:10931177-Humans, pubmed-meshheading:10931177-Mammals, pubmed-meshheading:10931177-Mice, pubmed-meshheading:10931177-Models, Molecular, pubmed-meshheading:10931177-Molecular Sequence Data, pubmed-meshheading:10931177-Mutagenesis, Site-Directed, pubmed-meshheading:10931177-Phospholipases A, pubmed-meshheading:10931177-Phospholipases A2, pubmed-meshheading:10931177-Phospholipids, pubmed-meshheading:10931177-Protein Conformation, pubmed-meshheading:10931177-Rats, pubmed-meshheading:10931177-Recombinant Proteins, pubmed-meshheading:10931177-Sequence Alignment, pubmed-meshheading:10931177-Sequence Homology, Amino Acid, pubmed-meshheading:10931177-Surface Plasmon Resonance, pubmed-meshheading:10931177-Thrombin, pubmed-meshheading:10931177-Thromboplastin
pubmed:year
2000
pubmed:articleTitle
Basic residues of human group IIA phospholipase A2 are important for binding to factor Xa and prothrombinase inhibition comparison with other mammalian secreted phospholipases A2.
pubmed:affiliation
Unité des Venins, Institut Pasteur, Paris, France.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't