Linked Life Data

15456490

Source:http://linkedlifedata.com/resource/pubmed/id/15456490

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2004-9-30
pubmed:abstractText
During normal hemostasis, the coagulation protease factor (F)XIa activates FIX. Hereditary deficiency of the FXIa precursor, FXI, is usually associated with reduced FXI protein in plasma, and circulating dysfunctional FXI variants are rare. We identified a patient with < 1% normal plasma FXI activity and normal levels of FXI antigen, who is homozygous for a FXI Gly555 to Glu substitution. Gly555 is two amino acids N-terminal to the protease active site serine residue, and is highly conserved among serine proteases. Recombinant FXI-Glu555 is activated normally by FXIIa and thrombin, and FXIa-Glu555 binds activated factor IX similarly to wild type FXIa (FXIa(WT)). When compared with FXIa(WT), FXIa-Glu555 activates factor IX at a greatly reduced rate ( approximately 400-fold), and is resistant to inhibition by antithrombin. Interestingly, FXIa(WT) and FXIa-Glu555 cleave the small tripeptide substrate S-2366 with comparable k(cat)s. Modeling indicates that the side chain of Glu555 significantly alters the electrostatic charge around the active site, and would sterically interfere with the interaction between the FXIa S2' site and the P2' residues on factor IX and antithrombin. FXI-Glu555 is the first reported example of a naturally occurring FXI variant with a significant defect in FIX activation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1538-7933
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1782-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Severe factor XI deficiency caused by a Gly555 to Glu mutation (factor XI-Glu555): a cross-reactive material positive variant defective in factor IX activation.
pubmed:affiliation
Amalia Biron Research Institute of Thrombosis and Hemostasis, Chaim Sheba Medical Center, Tel Hashomer, Israel.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural