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Structure-function Studies of Prothrombin Amrita, a Dysfunctional Prothrombin Characterized by Point Mutation at Arg553 → Gln

Publication Type : Journal Article

Thematic Areas : Nanosciences and Molecular Medicine

Publisher : International Journal of Biological Macromolecules

Source : International Journal of Biological Macromolecules, Elsevier B.V. (2018)

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Campus : Kochi

School : Center for Nanosciences, School of Biotechnology

Center : Amrita Center for Nanosciences and Molecular Medicine Move, Nanosciences

Department : Nanosciences and Molecular Medicine

Year : 2018

Abstract : A dysfunctional prothrombin gene characterized by novel point mutation at Arg553 to Gln residue in Deep vein thrombosis (DVT) patient which we designated as “Prothrombin Amrita” was previously reported from our lab. The mutation occurred at nucleotide 20030 in exon 14 and was confirmed by restriction enzyme digestion. Arg553 has been reported as one of the key residues for the binding of cofactor Na+ ion in the thrombin protein. Structural analysis revealed the molecular mechanism behind the coagulant form of thrombin due to point Arg553Gln mutation near the cofactor Na+ ion region. Molecular electrostatic potential maps and molecular dynamics (MD) simulation of the wild type and mutated thrombin showed the key role played by the Na+ ion for its coagulant mechanism by analysing the charge distribution and nature of the hydrogen bonding at the mutated region of interest. We observed maintenance of the fast or procoagulant form of dysfunctional prothrombin due to changes in the charge distribution by this mutation and thereby also keeping strong hydrogen bonding network revealed by MD simulation between prothrombin and Na+ ion. This molecular mechanism might be the main cause for DVT in patients with this dysfunctional prothrombin gene.

Cite this Research Publication : A. R. Melge, Prakash, O., S, S., Dr. Raja Biswas, Lalitha Biswas, and Dr. Gopi Mohan C., “Structure-Function Studies of Prothrombin Amrita, a Dysfunctional Prothrombin Characterized by Point Mutation at Arg553 → Gln”, International Journal of Biological Macromolecules, 2018.

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