Linked Life Data

17726015

Source:http://linkedlifedata.com/resource/pubmed/id/17726015

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
2007-10-22
pubmed:abstractText
Factor Xa (FXa) is a key protease of the coagulation pathway whose activity is known to be in part modulated by binding to factor Va (FVa) and sodium ions. Previous investigations have established that solvent-exposed, charged residues of the FXa alpha-helix 163-170 (h163-170), Arg(165) and Lys(169), participate in its binding to FVa. In the present study we aimed to investigate the role of the other residues of h163-170 in the catalytic functions of the enzyme. FX derivatives were constructed in which point mutations were made or parts of h163-170 were substituted with the corresponding region of either FVIIa or FIXa. Purified FXa derivatives were compared with wild-type FXa. Kinetic studies in the absence of FVa revealed that, compared with wild-type FXa, key functional parameters (catalytic activity toward prothrombin and tripeptidyl substrates and non-enzymatic interaction of a probe with the S1 site) were diminished by mutations in the NH(2)-terminal portion of h163-170. The defective amidolytic activity of these FXa derivatives appears to result from their impaired interaction with Na(+) because using a higher Na(+) concentration partially restored normal catalytic parameters. Furthermore, kinetic measurements with tripeptidyl substrates or prothrombin indicated that assembly of these FXa derivatives with an excess of FVa in the prothrombinase complex improves their low catalytic efficiency. These data indicate that residues in the NH(2)-terminal portion of the FVa-binding h163-170 are energetically linked to the S1 site and Na(+)-binding site of the protease and that residues Val(163) and Ser(167) play a key role in this interaction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31569-79
pubmed:meshHeading
pubmed-meshheading:17726015-Amino Acid Sequence, pubmed-meshheading:17726015-Amino Acid Substitution, pubmed-meshheading:17726015-Binding Sites, pubmed-meshheading:17726015-Catalysis, pubmed-meshheading:17726015-Crystallography, X-Ray, pubmed-meshheading:17726015-Factor Va, pubmed-meshheading:17726015-Factor Xa, pubmed-meshheading:17726015-Humans, pubmed-meshheading:17726015-Hydrogen Bonding, pubmed-meshheading:17726015-Kinetics, pubmed-meshheading:17726015-Models, Molecular, pubmed-meshheading:17726015-Molecular Sequence Data, pubmed-meshheading:17726015-Peptide Fragments, pubmed-meshheading:17726015-Point Mutation, pubmed-meshheading:17726015-Protein Binding, pubmed-meshheading:17726015-Protein Structure, Secondary, pubmed-meshheading:17726015-Prothrombin, pubmed-meshheading:17726015-Recombinant Proteins, pubmed-meshheading:17726015-Sequence Homology, Amino Acid, pubmed-meshheading:17726015-Serine, pubmed-meshheading:17726015-Sodium, pubmed-meshheading:17726015-Substrate Specificity, pubmed-meshheading:17726015-Thrombin, pubmed-meshheading:17726015-Valine
pubmed:year
2007
pubmed:articleTitle
Role of the alpha-helix 163-170 in factor Xa catalytic activity.
pubmed:affiliation
INSERM U770 and Université Paris-Sud, F-94276, Le Kremlin-Bicêtre, France.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't