Kruger W D, Cox D R
Department of Psychiatry, University of California at San Francisco 94143.
Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6614-8. doi: 10.1073/pnas.91.14.6614.
Human cystathionine beta-synthase (CBS; EC 4.2.1.22) deficiency results in a recessive genetic disorder whose clinical and biochemical manifestations vary greatly among affected individuals. In an effort to identify and analyze mutations in the human CBS gene, we have developed a yeast expression system for human CBS. We have cloned and sequenced a human cDNA that codes for CBS and have expressed the human CBS protein in yeast cells lacking endogenous CBS. The human enzyme produced in yeast is functional both in vitro and in vivo. We have also cloned and sequenced the yeast gene, CYS4, that codes for CBS. The predicted human and yeast CBS proteins are 38% identical and 72% similar to each other, as well as sharing significant similarity with bacterial cysteine synthase. These results demonstrate the evolutionary conservation of CBS and establish the utility of a yeast expression system for studying human CBS.
人类胱硫醚β-合酶（CBS；EC 4.2.1.22）缺乏会导致一种隐性遗传疾病，其临床和生化表现在受影响个体之间差异很大。为了鉴定和分析人类CBS基因中的突变，我们开发了一种用于人类CBS的酵母表达系统。我们克隆并测序了编码CBS的人类cDNA，并在缺乏内源性CBS的酵母细胞中表达了人类CBS蛋白。酵母中产生的人类酶在体外和体内均具有功能。我们还克隆并测序了编码CBS的酵母基因CYS4。预测的人类和酵母CBS蛋白彼此具有38%的同一性和72%的相似性，并且与细菌半胱氨酸合酶也具有显著的相似性。这些结果证明了CBS的进化保守性，并确立了酵母表达系统在研究人类CBS方面的实用性。
