Ash D E, Scolnick L R, Kanyo Z F, Vockley J G, Cederbaum S D, Christianson D W
Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Mol Genet Metab. 1998 Aug;64(4):243-9. doi: 10.1006/mgme.1998.2677.
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.
高精氨酸血症是一种罕见的常染色体隐性疾病，由肝脏I型精氨酸酶缺乏引起。在基因层面，精氨酸酶活性的这种缺乏是整个基因随机点突变的结果，这些突变导致蛋白质过早终止或替代突变。鉴于人类肝脏和大鼠肝脏酶之间高度的序列同源性，我们已将人类酶的患者和非患者突变映射到大鼠肝脏酶的结构上，以阐明这些突变精氨酸酶活性低的分子基础。在高精氨酸血症患者中鉴定出的突变通过损害活性位点残基、破坏蛋白质支架中的堆积相互作用和/或通过破坏精氨酸酶三聚体的组装来影响酶的结构和功能。
