rdf:type |
|
lifeskim:mentions |
umls-concept:C0015520,
umls-concept:C0032120,
umls-concept:C0033684,
umls-concept:C0043481,
umls-concept:C0072393,
umls-concept:C0164707,
umls-concept:C0205224,
umls-concept:C1148561,
umls-concept:C1167622,
umls-concept:C1549781,
umls-concept:C1879547
|
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
|