Abstract
BackgroundActivated Protein C (ProC) is an anticoagulant plasma serine protease which also plays an important role in controlling inflammation and cell proliferation. Several mutations of the gene are associated with phenotypic functional deficiency of protein C, and with the risk of developing venous thrombosis. Structure prediction and computational analysis of the mutants have proven to be a valuable aid in understanding the molecular aspects of clinical thrombophilia.ResultsWe have built a specialized relational database and a search tool for natural mutants of protein C. It contains 195 entries that include 182 missense and 13 stop mutations. A menu driven search engine allows the user to retrieve stored information for each variant, that include genetic as well as structural data and a multiple alignment highlighting the substituted position. Molecular models of variants can be visualized with interactive tools; PDB coordinates of the models are also available for further analysis. Furthermore, an automatic modelling interface allows the user to generate multiple alignments and 3D models of new variants.ConclusionProCMD is an up-to-date interactive mutant database that integrates phenotypical descriptions with functional and structural data obtained by computational approaches. It will be useful in the research and clinical fields to help elucidate the chain of events leading from a molecular defect to the related disease. It is available for academics at the URL .
Highlights
Activated Protein C (ProC) is an anticoagulant plasma serine protease which plays an important role in controlling inflammation and cell proliferation
Activated protein C (APC) is a vitamin K-dependent serine protease that plays a central role in the regulation of blood coagulation
APC binds to its cofactor protein S, and the complex inactivates the two cofactors involved in the clotting cascade, factors Va and factor VIIIa, leading to the efficient inhibition of the coagulation process
Summary
Activated Protein C (ProC) is an anticoagulant plasma serine protease which plays an important role in controlling inflammation and cell proliferation. Activated protein C (APC) is a vitamin K-dependent serine protease that plays a central role in the regulation of blood coagulation. It is the key component of an anticoagulant system that provides an essential mechanism in thrombosis prevention and in inflammatory response control. APC has direct and indirect anti-inflammatory actions. It prevents leukocyte rolling, tissue factor exposure and tumour (page number not for citation purposes). The anti-thrombotic and antiinflammatory actions of APC have been therapeutically exploited in severe sepsis [2]
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