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结核分枝杆菌中的一个腺苷酸环化酶假基因在鸟分枝杆菌中有一个功能同源物。

An adenylyl cyclase pseudogene in Mycobacterium tuberculosis has a functional ortholog in Mycobacterium avium.

作者信息

Shenoy A R, Srinivas A, Mahalingam M, Visweswariah S S

机构信息

Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India.

出版信息

Biochimie. 2005 Jun;87(6):557-63. doi: 10.1016/j.biochi.2005.01.017.

Abstract

A number of genes similar to mammalian Class III nucleotide cyclases are found in mycobacteria, and biochemical characterization of some of these proteins has indicated that they code for adenylyl cyclases, with properties similar to the mammalian enzymes. Our earlier bioinformatic analysis had predicted that the Rv1120c gene in Mycobacterium tuberculosis is a pseudogene, while analysis of the genome of Mycobacterium avium indicated the presence of a functional ortholog. We therefore cloned and expressed Rv1120c and its ortholog from M. avium, Ma1120, in Escherichia coli, and find that while the protein from M. tuberculosis is misfolded and found in inclusion bodies, Ma1120 is expressed to high levels as a functional adenylyl cyclase. Sequence analysis of Ma1120 indicates interesting variations in critical amino acids that are known to be important for catalytic activity. Ma1120 is maximally active in the presence of MnATP as substrate ((app)Km approximately 400 microM), and is inhibited by P-site inhibitors (IC50 of 2',5'-dideoxy-3'-adenosine triphosphate approximately 730 nM) and tyrphostins (IC50 approximately 36 microM) in a manner similar to the mammalian enzymes. This therefore represents the first Class III cyclase biochemically characterized from M. avium, and the absence of a functional ortholog in M. tuberculosis suggests a unique role for this enzyme in M. avium.

摘要

在分枝杆菌中发现了一些与哺乳动物Ⅲ类核苷酸环化酶相似的基因,对其中一些蛋白质的生化特性分析表明,它们编码腺苷酸环化酶,其特性与哺乳动物的酶相似。我们早期的生物信息学分析预测结核分枝杆菌中的Rv1120c基因是一个假基因,而鸟分枝杆菌基因组分析表明存在一个功能直系同源基因。因此,我们在大肠杆菌中克隆并表达了来自结核分枝杆菌的Rv1120c及其来自鸟分枝杆菌的直系同源基因Ma1120,发现结核分枝杆菌的蛋白质错误折叠并存在于包涵体中,而Ma1120作为一种功能性腺苷酸环化酶高水平表达。Ma1120的序列分析表明,已知对催化活性重要的关键氨基酸存在有趣的变异。Ma1120以MnATP作为底物时活性最高((表观)Km约为400μM),并以与哺乳动物酶相似的方式被P位点抑制剂(2',5'-二脱氧-3'-三磷酸腺苷的IC50约为730 nM)和酪氨酸磷酸化抑制剂(IC50约为36μM)抑制。因此,这代表了首次对来自鸟分枝杆菌的Ⅲ类环化酶进行生化特性鉴定,结核分枝杆菌中缺乏功能性直系同源基因表明该酶在鸟分枝杆菌中具有独特作用。

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