The structure and computational analysis of Mycobacterium tuberculosis protein CitE suggest a novel enzymatic function
The structure and computational analysis of Mycobacterium tuberculosis protein CitE suggest a novel enzymatic function
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DOI：
10.1016/j.jmb.2006.09.086
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发表时间：
2007-01-12
影响因子：
5.6
通讯作者：
Eisenberg, David
中科院分区：
文献类型：
--
作者：
Goulding, Celia W.;Bowers, Peter M.;Eisenberg, David
脂肪酸的生物合成是结核分枝杆菌生存所必需的，乙酰辅酶A（acetyl-CoA）是该途径中的重要前体。我们测定了M的3-1）晶体结构。结核病柠檬酸裂解酶β-亚基（CitE），其如所注释的应将蛋白质结合的柠檬酰-CoA裂解成草酰乙酸和蛋白质结合的CoA衍生物。CitE结构具有（β/α）（8）TIM桶折叠和额外的α-螺旋，并且是三聚体。我们已经确定了三元复合物结合草酰乙酸和镁，揭示了一些保守的残基参与催化。细菌柠檬酸裂解酶是一个由三个亚基组成的复合物，而M.结核分枝杆菌基因组中不含该复合物的α和γ亚基，这意味着M.结核病CitE与其他细菌CitE蛋白的作用不同。对来自168个完全测序的生物体的包含CitE蛋白的基因簇的分析使我们鉴定出一组在M.结核病、褐家鼠、智人和小家鼠。我们提出了一个新的酶功能的M。结核病CitE在脂肪酸生物合成中类似于细菌柠檬酸裂解酶，但产生乙酰辅酶A而不是蛋白质结合的辅酶A衍生物。(c)2006爱思唯尔有限公司保留所有权利。
Fatty acid biosynthesis is essential for the survival of Mycobacterium tuberculosis and acetyl-coenzyme A (acetyl-CoA) is an essential precursor in this pathway. We have determined the 3-1) crystal structure of M. tuberculosis citrate lyase beta-subunit (CitE), which as annotated should cleave protein bound citryl-CoA to oxaloacetate and a protein-bound CoA derivative. The CitE structure has the ( beta/alpha)(8) TIM barrel fold with an additional a-helix, and is trimeric. We have determined the ternary complex bound with oxaloacetate and magnesium, revealing some of the conserved residues involved in catalysis. While the bacterial citrate lyase is a complex with three subunits, the M. tuberculosis genome does not contain the alpha and gamma subunits of this complex, implying that M. tuberculosis CitE acts differently from other bacterial CitE proteins. The analysis of gene clusters containing the CitE protein from 168 fully sequenced organisms has led us to identify a grouping of functionally related genes preserved in M. tuberculosis, Rattus norvegicus, Homo sapiens, and Mus musculus. We propose a novel enzymatic function for M. tuberculosis CitE in fatty acid biosynthesis that is analogous to bacterial citrate lyase but producing acetyl-CoA rather than a protein-bound CoA derivative. (c) 2006 Elsevier Ltd. All rights reserved.