S-adenosylhomocysteine hydrolase (AHCY) deficiency: two novel mutations with lethal outcome.

ABSTRACT: This paper reports studies of two novel, allelic missense mutations found in the S-adenosylhomocysteine hydrolase (AHCY) gene from a new case of AHCY deficiency in an infant girl who died at age four months. The mutations lead to replacement of arginine with cysteine (p.Arg49Cys) and aspartic acid with glycine (p.Asp86Gly). Functional analysis of recombinant proteins containing the mutations detected showed that both dramatically reduce AHCY activity. The p.Arg49Cys mutant protein forms intermolecular disulphide bonds, leading to macromolecular structures that can be prevented by reducing agent DTT. The p.Asp86Gly protein tends to form enzymatically inactive aggregates and the loss of a single negative charge as a result of the mutation is involved in enzyme inactivation. We show that repl

SUBMITTER: Vugrek O 

PROVIDER: S-EPMC2876820 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature