高丝氨酸脱氢酶催化机理的结构基础。

Vikas Navratna, Govardhan Reddy, Balasubramanian Gopal
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引用次数: 13

摘要

同丝氨酸脱氢酶(HSD)是天冬氨酸途径中的一种氧化还原酶。该酶协调代谢途径的一个关键分支点,导致细菌细胞壁成分(如l-赖氨酸和m-DAP)以及其他氨基酸(如l-苏氨酸、l-蛋氨酸和l-异亮氨酸)的合成。本文报道了HSD反应机制中氢化物转移步骤的结构原理。测定了金黄色葡萄球菌HSD在不同pH条件下的结构,以了解在碱性pH条件下酶活性增强的基础。晶体结构分析表明,位于催化和辅因子结合位点界面的Lys105可以介导反应机理的氢化物转移步骤。Lys105的作用随后通过突变分析得到证实。综上所述,这些研究揭示了保守的水分子和赖氨酸残基在底物和辅因子之间氢化物转移中的作用。
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Structural basis for the catalytic mechanism of homoserine dehydrogenase.

Homoserine dehydrogenase (HSD) is an oxidoreductase in the aspartic acid pathway. This enzyme coordinates a critical branch point of the metabolic pathway that leads to the synthesis of bacterial cell-wall components such as L-lysine and m-DAP in addition to other amino acids such as L-threonine, L-methionine and L-isoleucine. Here, a structural rationale for the hydride-transfer step in the reaction mechanism of HSD is reported. The structure of Staphylococcus aureus HSD was determined at different pH conditions to understand the basis for the enhanced enzymatic activity at basic pH. An analysis of the crystal structure revealed that Lys105, which is located at the interface of the catalytic and cofactor-binding sites, could mediate the hydride-transfer step of the reaction mechanism. The role of Lys105 was subsequently confirmed by mutational analysis. Put together, these studies reveal the role of conserved water molecules and a lysine residue in hydride transfer between the substrate and the cofactor.

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