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首页> 外文期刊>Biochemistry >The 1.9 A Crystal Structure of Alanine Racemase from Mycobacterium tuberculosis Contains a Conserved Entryway into the Active Site(,).
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The 1.9 A Crystal Structure of Alanine Racemase from Mycobacterium tuberculosis Contains a Conserved Entryway into the Active Site(,).

机译：1.9结核分枝杆菌丙氨酸消旋酶的晶体结构包含进入活性位点的保守入口。

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摘要

We report the crystal structure of alanine racemase from Mycobacterium tuberculosis (Alr(Mtb)()) at 1.9 A resolution. In our structure, Alr(Mtb)() is found to be a dimer formed by two crystallographically different monomers, each comprising 384 residues. The domain makeup of each monomer is similar to that of Bacillus and Pseudomonas alanine racemases and includes both an alpha/beta-barrel at the N-terminus and a C-terminus primarily made of beta-strands. The hinge angle between these two domains is unique for Alr(Mtb)(), but the active site geometry is conserved. In Alr(Mtb)(), the PLP cofactor is covalently bound to the protein via an internal aldimine bond with Lys42. No guest substrate is noted in its active site, although some residual electron density is observed in the enzyme's active site pocket. Analysis of the active site pocket, in the context of other known alanine racemases, allows us to propose the inclusion of conserved residues found at the entrance to the binding pocket as additional targets in ongoing structure-aided drug design efforts. Also, as observed in other alanine racemase structures, PLP adopts a conformation that significantly distorts the planarity of the extended conjugated system between the PLP ring and the internal aldimine bond.
机译：我们从1.9 A分辨率报告从结核分枝杆菌（Alr（Mtb）（））丙氨酸消旋酶的晶体结构。在我们的结构中，发现Alr（Mtb）（）是由两个晶体学不同的单体形成的二聚体，每个单体包含384个残基。每个单体的结构域组成类似于芽孢杆菌和假单胞菌丙氨酸消旋体，并且在N端和主要由β链制成的C端都包括α/β-桶。对于Alr（Mtb）（），这两个域之间的铰链角是唯一的，但活动位置的几何形状是守恒的。在Alr（Mtb）（）中，PLP辅因子通过与Lys42的内部醛亚胺键共价结合到蛋白质上。尽管在酶的活性位点口袋中观察到一些残留的电子密度，但在其活性位点没有观察到客体底物。在其他已知的丙氨酸消旋体的背景下，对活性位点袋的分析使我们建议将结合袋入口处发现的保守残基包括在内，作为正在进行的结构辅助药物设计工作中的其他目标。同样，如在其他丙氨酸消旋酶结构中观察到的，PLP所采用的构象会严重扭曲PLP环与内部醛亚胺键之间的扩展共轭体系的平面度。

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