Molecular basis of hyperargininemia: structure-function consequences of mutations in human liver arginase.

Autor:	Ash DE; Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. deash@astro.ocis.temple.edu, Scolnick LR, Kanyo ZF, Vockley JG, Cederbaum SD, Christianson DW
Jazyk:	angličtina
Zdroj:	Molecular genetics and metabolism [Mol Genet Metab] 1998 Aug; Vol. 64 (4), pp. 243-9.
DOI:	10.1006/mgme.1998.2677
Abstrakt:	Hyperargininemia is a rare autosomal recessive disorder that results from a deficiency of hepatic type I arginase. At the genetic level, this deficiency in arginase activity is a consequence of random point mutations throughout the gene that lead to premature termination of the protein or to substitution mutations. Given the high degree of sequence homology between human liver and rat liver enzymes, we have mapped both patient and nonpatient mutations of the human enzyme onto the structure of the rat liver enzyme to rationalize the molecular basis for the low activities of these mutant arginases. Mutations identified in hyperargininemia patients affect the structure and function of the enzyme by compromising active-site residues, packing interactions in the protein scaffolding, and/or quaternary structure by destabilizing the assembly of the arginase trimer. (Copyright 1998 Academic Press.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Full Text from ScienceDirect