Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2009-7-1
pubmed:abstractText
Protein S (PS) is a cofactor for activated protein C (APC), which inactivates coagulation factors (F) Va and VIIIa. Deficiency of protein C or PS is associated with risk of thrombosis. We found that PS also has APC-independent anticoagulant activity (PS-direct) and directly inhibits thrombin generated by FXa/FVa (prothrombinase complex). Here we report that PS contains Zn(2+) that is required for PS-direct and that is lost during certain purification procedures. Immunoaffinity-purified PS contained 1.4 +/- 0.6 Zn(2+)/mol, whereas MonoQ-purified and commercial PS contained 0.15 +/- 0.15 Zn(2+)/mol. This may explain the controversy regarding the validity of PS-direct. Zn(2+) content correlated positively with PS-direct in prothrombinase assays and clotting assays, but APC-cofactor activity of PS was independent of Zn(2+) content. PS-direct and Zn(2+) were restored to inactive PS under mildly denaturing conditions. Conversely, o-phenanthroline reversibly impaired the PS-direct of active PS. Zn(2+)-containing PS bound FXa more efficiently (K(d)(app)=9.3 nM) than Zn(2+)-deficient PS (K(d)(app)=110 nM). PS bound TFPI efficiently, independently of Zn(2+) content (K(d)(app)=21 nM). Antibodies that block PS-direct preferentially recognized Zn(2+)-containing PS, suggesting conformation differences at or near the interface of 2 laminin G-like domains near the PS C terminus. Thus, Zn(2+) is required for PS-direct and efficient FXa binding and may play a role in stabilizing PS conformation.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-10593904, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-10675319, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-10708848, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-11276089, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-11467946, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-11802720, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-11941507, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-12218057, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-12228253, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-1245477, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-12490286, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-12695512, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-12730108, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-15456488, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-16240665, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-16420570, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-16488980, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-16757484, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-16824189, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-17280606, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-18784085, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-18824642, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-2145284, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-2148275, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-6226944, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-6238642, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-6892911, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-8063724, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-8146182, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-8428962, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-8621478, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-9461535, http://linkedlifedata.com/resource/pubmed/commentcorrection/19244162-9490026
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2244-53
pubmed:dateRevised
2011-6-16
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Plasma protein S contains zinc essential for efficient activated protein C-independent anticoagulant activity and binding to factor Xa, but not for efficient binding to tissue factor pathway inhibitor.
pubmed:affiliation
Department of Molecular and Experimental Medicine, MEM276, Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA. heeb@scripps.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural