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结核分枝杆菌分支酸合酶的结晶及初步X射线晶体学分析

Crystallization and preliminary X-ray crystallographic analysis of chorismate synthase from Mycobacterium tuberculosis.

作者信息

Dias Marcio Viniciusbertacine, Ely Fernanda, Canduri Fernanda, Pereira José Henrique, Frazzon Jeverson, Basso Luiz Augusto, Palma Mário Sérgio, de Azevedo Walter Filgueira, Santos Diógenes Santiago

机构信息

Departamento de Física, UNESP, São José do Rio Preto, SP 15054-000, Brazil.

出版信息

Acta Crystallogr D Biol Crystallogr. 2004 Nov;60(Pt 11):2003-5. doi: 10.1107/S0907444904019869. Epub 2004 Oct 20.

Abstract

The enzymes of the shikimate pathway are potential targets for the development of new therapies because they are essential for bacteria but absent from mammals. The last step in this pathway is performed by chorismate synthase (CS), which catalyzes the conversion of 5-enolpyruvylshikimate-3-phosphate to chorismate. Optimization of crystallization trials allowed the crystallization of homogeneous recombinant CS from Mycobacterium tuberculosis (MtCS). The crystals of MtCS belong to space group P6(4)22 (or P6(2)22) and diffract to 2.8 A resolution, with unit-cell parameters a = b = 129.7, c = 156.8 A. There are two molecules in the asymmetric unit. Molecular-replacement trials were not successful. Heavy-atom derivative screening is in progress.

摘要

莽草酸途径的酶是开发新疗法的潜在靶点,因为它们对细菌至关重要,但在哺乳动物中不存在。该途径的最后一步由分支酸合酶(CS)完成,它催化5-烯醇丙酮酸莽草酸-3-磷酸转化为分支酸。优化结晶试验使得来自结核分枝杆菌的重组CS(MtCS)能够均匀结晶。MtCS的晶体属于空间群P6(4)22(或P6(2)22),衍射分辨率达到2.8 Å,晶胞参数a = b = 129.7,c = 156.8 Å。不对称单元中有两个分子。分子置换试验未成功。重原子衍生物筛选正在进行中。

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