Structure-function assessment of the role of the helical stack domain in the properties of human recombinant protein C and activated protein C

Biochemistry ◽  
1995 ◽  
Vol 34 (25) ◽  
pp. 8082-8090 ◽  
Author(s):  
William T. Christiansen ◽  
Jie-Ping Geng ◽  
Francis J. Castellino
2004 ◽  
Vol 32 (Supplement) ◽  
pp. S262-S265 ◽  
Author(s):  
Koji Suzuki ◽  
Esteban Cesar Gabazza ◽  
Tatsuya Hayashi ◽  
Haruhiko Kamada ◽  
Yukihiko Adachi ◽  
...  

2004 ◽  
Vol 24 (6) ◽  
pp. 40-45
Author(s):  
Janice Tazbir

Thorax ◽  
2009 ◽  
Vol 64 (2) ◽  
pp. 114-120 ◽  
Author(s):  
M R Looney ◽  
C T Esmon ◽  
M A Matthay

2011 ◽  
Vol 106 (12) ◽  
pp. 1034-1045. ◽  
Author(s):  
Karin Wildhagen ◽  
Esther Lutgens ◽  
Sarah Loubele ◽  
Hugo ten Cate ◽  
Gerry Nicolaes

SummaryProtein C is the central enzyme of the natural anticoagulant pathway and its activated form APC (activated protein C) is able to proteolyse non-active as well as active coagulation factors V and VIII. Proteolysis renders these cofactors inactive, resulting in an attenuation of thrombin formation and overall down-regulation of coagulation. Presences of the APC cofactor, protein S, thrombomodulin, endothelial protein C receptor and a phospholipid surface are important for the expression of anticoagulant APC activity. Notably, APC also has direct cytoprotective effects on cells: APC is able to protect the endothelial barrier function and expresses anti-inflammatory and anti-apoptotic activities. Exact molecular mechanisms have thus far not been completely described but it has been shown that both the protease activated receptor 1 and EPCR are essential for the cytoprotective activity of APC. Recently it was shown that also other receptors like sphingosine 1 phosphate receptor 1, Cd11b/CD18 and tyrosine kinase with immunoglobulin-like and EGFlike domains 2 are likewise important for APC signalling. Mutagenesis studies are being performed to map the various APC functions and interactions onto its 3D structure and to dissect anticoagulant and cytoprotective properties. The results of these studies have provided a wealth of structure-function information. With this review we describe the state-of-the-art of the intricate structure-function relationships of APC, a protein that harbours several important functions for the maintenance of both humoral and tissue homeostasis.Lessons from natural and engineered mutations


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