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首页> 外文期刊>Acta crystallographica. Section D, Biological crystallography. >Structure and inhibition of subunit I of the anthranilate synthase complex of Mycobacterium tuberculosis and expression of the active complex
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Structure and inhibition of subunit I of the anthranilate synthase complex of Mycobacterium tuberculosis and expression of the active complex

机译：我的亚基的结构和抑制邻氨基苯甲酸盐合成酶复杂的分枝杆菌结核病和活跃的复杂的表情

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摘要

The tryptophan-biosynthesis pathway is essential for Mycobacterium tuberculosis (Mtb) to cause disease, but not all of the enzymes that catalyse this pathway in this organism have been identified. The structure and function of the enzyme complex that catalyses the first committed step in the pathway, the anthranilate synthase (AS) complex, have been analysed. It is shown that the open reading frames Rv1609 (trpE) and Rv0013 (trpG) encode the chorismate-utilizing (AS-I) and glutamine amidotransferase (AS-II) subunits of the AS complex, respectively. Biochemical assays show that when these subunits are co-expressed a bifunctional AS complex is obtained. Crystallization trials on Mtb-AS unexpectedly gave crystals containing only AS-I, presumably owing to its selective crystallization from solutions containing a mixture of the AS complex and free AS-I. The three-dimensional structure reveals that Mtb-AS-I dimerizes via an interface that has not previously been seen in AS complexes. As is the case in other bacteria, it is demonstrated that Mtb-AS shows cooperative allosteric inhibition by tryptophan, which can be rationalized based on interactions at this interface. Comparative inhibition studies on Mtb-AS-I and related enzymes highlight the potential for single inhibitory compounds to target multiple chorismate-utilizing enzymes for TB drug discovery.
机译：tryptophan-biosynthesis通路是至关重要的结核分枝杆菌(Mtb)的原因疾病,但并不是所有的酶催化这条通路在这个有机体识别。酶催化作用第一个提交的复杂一步通路,邻氨基苯甲酸盐合成酶(作为)复杂,进行了分析。的开放阅读框架Rv1609 (trpE)和chorismate-utilizing Rv0013 (trpG)编码(我)和谷氨酰胺amidotransferase(在与ii)复杂的子单元,分别。生化分析表明,当这些子单元中的一个双功能复杂吗获得的。竟给晶体只包含我,大概由于其选择性结晶从解决方案包含的混合物复杂的和自由的我。通过一个结构表明,Mtb-AS-I二聚界面,以前没有发现过复合物。是证明Mtb-AS显示合作变构由色氨酸抑制,可以基于交互的合理化接口。Mtb-AS-I和相关酶突出潜在的抑制化合物目标多个chorismate-utilizing酶结核病药物发现。

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