Theoretical and experimental study of the D2194G mutation in the C2 domain of coagulation factor V.

ABSTRACT: Coagulation factor V (FV) is a large plasma glycoprotein with functions in both the pro- and anticoagulant pathways. In carriers of the so-called R2-FV haplotype, the FV D2194G mutation, in the C2 membrane-binding domain, is associated with low expression levels, suggesting a potential folding/stability problem. To analyze the molecular mechanisms potentially responsible for this in vitro phenotype, we used molecular dynamics (MD) and continuum electrostatic calculations. Implicit solvent simulations were performed on the x-ray structure of the wild-type C2 domain and on a model of the D2194G mutant. Because D2194 is located next to a disulfide bond (S-S bond), MD calculations were also performed on S-S bond depleted structures. D2194 is part of a salt-bridge network and investigations of

SUBMITTER: Miteva MA 

PROVIDER: S-EPMC1303816 | biostudies-literature | 2004 Jan

REPOSITORIES: biostudies-literature