Abstract
Thrombin is a Na+-activated, allosteric serine protease that plays opposing functional roles in blood coagulation. Binding of Na+ is the major driving force behind the procoagulant, prothrombotic, and signaling functions of the enzyme, but is dispensable for cleavage of the anticoagulant protein C. The anticoagulant function of thrombin is under the allosteric control of the cofactor thrombomodulin. Recent structural advances have shed light on the remarkable molecular plasticity of this enzyme and the molecular underpinnings of thrombin allostery mediated by binding to exosite I and the Na+ site. Thrombin exists in three forms - E∗, E, and E:Na+, which interconvert under the influence of ligand binding to distinct domains. The transition between the Na+-free slow form E and the Na+-bound fast form E:Na+ involves the structure of the enzyme as a whole, and so does the interconversion between the two Na+-free forms E∗and E. E∗is most likely an inactive form of thrombin, unable to interact with Na+ and substrate.
| Original language | English (US) |
|---|---|
| Title of host publication | Thrombin: Physiology and Disease |
| Publisher | Springer US |
| Pages | 1-18 |
| Number of pages | 18 |
| ISBN (Print) | 9780387096377, 9780387096360 |
| DOIs | |
| State | Published - 2009 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Medicine(all)
Cite this
Thrombin : Structure, functions, and regulation. / Cera, Enrico Di; Gruber, Andras.
Thrombin: Physiology and Disease. Springer US, 2009. p. 1-18.Research output: Chapter in Book/Report/Conference proceeding › Chapter
}
TY - CHAP
T1 - Thrombin
T2 - Structure, functions, and regulation
AU - Cera, Enrico Di
AU - Gruber, Andras
PY - 2009
Y1 - 2009
N2 - Thrombin is a Na+-activated, allosteric serine protease that plays opposing functional roles in blood coagulation. Binding of Na+ is the major driving force behind the procoagulant, prothrombotic, and signaling functions of the enzyme, but is dispensable for cleavage of the anticoagulant protein C. The anticoagulant function of thrombin is under the allosteric control of the cofactor thrombomodulin. Recent structural advances have shed light on the remarkable molecular plasticity of this enzyme and the molecular underpinnings of thrombin allostery mediated by binding to exosite I and the Na+ site. Thrombin exists in three forms - E∗, E, and E:Na+, which interconvert under the influence of ligand binding to distinct domains. The transition between the Na+-free slow form E and the Na+-bound fast form E:Na+ involves the structure of the enzyme as a whole, and so does the interconversion between the two Na+-free forms E∗and E. E∗is most likely an inactive form of thrombin, unable to interact with Na+ and substrate.
AB - Thrombin is a Na+-activated, allosteric serine protease that plays opposing functional roles in blood coagulation. Binding of Na+ is the major driving force behind the procoagulant, prothrombotic, and signaling functions of the enzyme, but is dispensable for cleavage of the anticoagulant protein C. The anticoagulant function of thrombin is under the allosteric control of the cofactor thrombomodulin. Recent structural advances have shed light on the remarkable molecular plasticity of this enzyme and the molecular underpinnings of thrombin allostery mediated by binding to exosite I and the Na+ site. Thrombin exists in three forms - E∗, E, and E:Na+, which interconvert under the influence of ligand binding to distinct domains. The transition between the Na+-free slow form E and the Na+-bound fast form E:Na+ involves the structure of the enzyme as a whole, and so does the interconversion between the two Na+-free forms E∗and E. E∗is most likely an inactive form of thrombin, unable to interact with Na+ and substrate.
UR - http://www.scopus.com/inward/record.url?scp=84899878495&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899878495&partnerID=8YFLogxK
U2 - 10.1007/978-0-387-09637-7_1
DO - 10.1007/978-0-387-09637-7_1
M3 - Chapter
AN - SCOPUS:84899878495
SN - 9780387096377
SN - 9780387096360
SP - 1
EP - 18
BT - Thrombin: Physiology and Disease
PB - Springer US
ER -