A PHENYLALANINE-402 TO LEUCINE MUTATION IS RESPONSIBLE FOR A STABLE INACTIVE CONFORMATION OF ANTITHROMBIN

作者：EMMERICH J^*; CHADEUF G; COETZEE MJ; ALHENCGELAS M; FIESSINGER JN; AIACH M

来源：Thrombosis Research, 1994, 76(3): 307-315.

DOI：10.1016/0049-3848(94)90202-X

• ANTITHROMBIN
• CONFORMATION
• MUTATION

In a South African family with antithrombin deficiency and unexplained thrombosis, genomic DNA analysis revealed a substitution of Phe 402 by Leu. This mutation involves an amino acid located in the carboxyterminal side of the antithrombin reactive loop and has already been observed in a French family (antithrombin Maisons-Laffitte). In both cases, the expression of the mutation is pleiotropic, i.e. results in a reduction in the circulating concentration of antithrombin and impairs both its anti-thrombin activity and its ability to bind heparin. The effect of a denaturing agent (sodium dodecyl sulfate) on the recognition of the plasma antithrombin by a polyclonal antibody was studied in an immuno-enzymatic assay. The Phe to Leu mutation decreased the sensitivity to denaturation, suggesting that the mutation increases the stability of the protein. Wether this stable conformation is due to a partial insertion of the amino-terminal side of the reactive loop, which would explain how both protease binding and heparin binding are affected, remains to be determined.

• 出版日期1994-11-1