Mechanism of Substrate Recognition and Catalysis of the Haloalkanoic Acid Dehalogenase Family Member α-Phosphoglucomutase.
Mechanism of Substrate Recognition and Catalysis of the Haloalkanoic Acid Dehalogenase Family Member α-Phosphoglucomutase.
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卤代链烷酸脱卤酶家族成员α-磷酸葡萄糖变位酶的底物识别和催化机制。
DOI：
10.1021/acs.biochem.8b00396
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发表时间：
2018
期刊：
影响因子：
2.9
通讯作者：
Dunaway-Mariano,Debra
中科院分区：
文献类型：
--
作者：
Zhang,Chunchun;Allen,KarenN;Dunaway-Mariano,Debra
α-磷酸葡萄糖变位酶（α-PGM）在其磷酸化状态下催化α-d-葡萄糖1-磷酸和α-d-葡萄糖6-磷酸的相互转化。乳酸乳球菌（Lactococcus lactis）的αPGM是卤代链烷酸脱卤酶（HAD）家族的C2B型成员，由Rossmann折叠催化结构域和插入的α/β折叠帽结构域组成。活性位点形成于畴-畴界面处。在此，我们报告的结果，从动力学为基础的研究ofL。lactisαPGM催化，其通过Asp 8与α G1 P的自催化磷酸化、αG1，6 bisP在磷酸化L1-α PGM催化的α G1 P转化为G6 P中的中间作用以及αG1，6 bisP中间体通过解离至溶剂和重新结合而重新定向来证明酶活化。为了深入了解L的结构决定因素。测定了lactisαPGM底物识别和催化、金属辅因子和底物特异性，以及活性位点残基对催化效率的贡献。最后，对L. lactisαPGM与HAD家族的磷酸变位酶L进行了比较。乳酸β-磷酸葡萄糖变位酶和真核生物α-磷酸甘露糖变位酶的研究，以提供对HAD家族磷酸酶的磷酸己糖变位酶进化的深入了解。
α-Phosphoglucomutase (αPGM), in its phosphorylated state, catalyzes the interconversion of α-d-glucose 1-phosphate and α-d-glucose 6-phosphate. The αPGM ofLactococcus lactisis a type C2B member of the haloalkanoic acid dehalogenase (HAD) enzyme family and is comprised of a Rossmann-fold catalytic domain and inserted α/β-fold cap domain. The active site is formed at the domain–domain interface. Herein, we report the results from a kinetic-based study ofL. lactisαPGM catalysis, which demonstrate enzyme activation by autocatalyzed phosphorylation of Asp8 with αG1P, the intermediacy of αG1,6bisP in the phosphoLl-αPGM-catalyzed conversion of αG1P to G6P, and the reorientation of the αG1,6bisP intermediate via dissociation to solvent and rebinding. In order to provide insight into the structural determinants ofL. lactisαPGM substrate recognition and catalysis, metal cofactor and substrate specificities were determined as were the contributions made by active-site residues toward catalytic efficiency. Lastly, the structure and catalytic mechanism ofL. lactisαPGM are compared with those of HAD family phosphomutasesL. lactisβ-phosphoglucomutase and eukayotic α-phosphomannomutase to provide insight into the evolution of phosphohexomutases from HAD family phosphatases.
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影响因子：
2.9
作者：
Dai, Jianying;Finci, Lorenzo;Zhang, Chunchun;Lahiri, Sushmita;Zhang, Guofeng;Peisach, Ezra;Allen, Karen N.;Dunaway-Mariano, Debra
通讯作者：
Dunaway-Mariano, Debra
影响因子：
2.9
作者：
Morais, MC;Zhang, WH;Allen, KN
通讯作者：
Allen, KN
影响因子：
4
作者：
N. Sanfélix-Haywood;J.M. Coll‐Marqués-;M. J. Yebra
通讯作者：
N. Sanfélix-Haywood;J.M. Coll‐Marqués-;M. J. Yebra
影响因子：
2.9
作者：
NEEDHAM, JV;CHEN, TY;FALKE, JJ
通讯作者：
FALKE, JJ
影响因子：
2.9
作者：
Dai, Jianying;Wang, Liangbing;Dunaway-Mariano, Debra
通讯作者：
Dunaway-Mariano, Debra