Perry S, Harries H, Scholfield C, Lock T, King L, Gibson G, Goldfarb P
Molecular Toxicology Research Group, School of Biological Sciences, University of Surrey, Guildford, UK.
FEBS Lett. 1995 Mar 6;360(3):277-80. doi: 10.1016/0014-5793(95)00123-q.
Kidney cysteine conjugate beta-lyase (glutamine transaminase K, kyneurenine aminotransferase, EC 2.6.1.64) metabolises the cysteine conjugates of certain halogenated alkenes and alkanes to form reactive metabolites which can produce nephrotoxicity and neurotoxicity in experimental animals and man. Using a combination of hybridisation screening and PCR techniques we have isolated a full-length cDNA for human kidney cysteine conjugate beta-lyase. Comparison of the deduced amino acid sequence with that of the rat enzyme indicated an 82% overall similarity, with 90% similarity around the pyridoxal phosphate binding site, many of the changes being conservative in nature. Expression of the cDNA in Cos-1 cells resulted in the production of a cytosolic enzyme which showed both cysteine conjugate beta-lyase and glutamine transminase K activity. Preliminary mapping of the gene for human cysteine conjugate beta-lyase by PCR analysis of genomic DNA from human-rodent hybrid cells indicated that it is located on human chromosome 9.
肾半胱氨酸共轭β-裂合酶（谷氨酰胺转氨酶K、犬尿氨酸转氨酶，EC 2.6.1.64）可将某些卤代烯烃和烷烃的半胱氨酸共轭物代谢，形成活性代谢产物，这些产物可在实验动物和人类中产生肾毒性和神经毒性。通过杂交筛选和PCR技术相结合，我们分离出了人肾半胱氨酸共轭β-裂合酶的全长cDNA。将推导的氨基酸序列与大鼠酶的序列进行比较，结果显示总体相似性为82%，在磷酸吡哆醛结合位点周围的相似性为90%，许多变化本质上是保守的。该cDNA在Cos-1细胞中的表达产生了一种胞质酶，该酶同时具有半胱氨酸共轭β-裂合酶和谷氨酰胺转氨酶K活性。通过对人-啮齿动物杂交细胞的基因组DNA进行PCR分析，初步绘制了人半胱氨酸共轭β-裂合酶基因图谱，结果表明它位于人类9号染色体上。
