Substrate distortion contributes to the catalysis of orotidine 5'-monophosphate decarboxylase.
Substrate distortion contributes to the catalysis of orotidine 5'-monophosphate decarboxylase.
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DOI：
10.1021/ja408197k
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发表时间：
2013-11-20
影响因子：
15
通讯作者：
Miki K
中科院分区：
文献类型：
--
作者：
Fujihashi M;Ishida T;Kuroda S;Kotra LP;Pai EF;Miki K
乳清酸核苷5 '-单磷酸脱羧酶（ODCase）将乳清酸核苷5'-单磷酸（OMP）脱羧为尿苷5 '-单磷酸（UMP）加速17个数量级。八个新的晶体结构与配体类似物相结合的计算分析的酶的短寿命的中间体和内在的电子能量扭曲的基板和其他配体提高我们的理解仍然有争议的讨论反应机制。在它们各自的复合物中，6-甲基-UMP显示其甲基取代基键的显著扭曲，6-氨基-UMP显示K72和C6取代基之间对接近D 70的位置的竞争，并且OMP的甲酯和乙酯都诱导羧酸酯基团取代基旋转出嘧啶环的平面。酶-底物（ES）复合物的MD和QM/MM计算也显示羧酸基团和嘧啶环之间的键被扭曲，扭曲导致ΔΔG值降低10-15%。这些结果与ODCase一致，其使用底物畸变以及过渡态稳定，主要由K72在其催化OMP脱羧反应中发挥作用。
Orotidine 5'-monophosphate decarboxylase (ODCase) accelerates the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP) by 17 orders of magnitude. Eight new crystal structures with ligand analogues combined with computational analyses of the enzyme’s short-lived intermediates and the intrinsic electronic energies to distort the substrate and other ligands improve our understanding of the still controversially discussed reaction mechanism. In their respective complexes, 6-methyl-UMP displays significant distortion of its methyl substituent bond, 6-amino-UMP shows the competition between the K72 and C6 substituents for a position close to D70, and the methyl- and ethyl-ester of OMP both induce rotation of the carboxylate group substituent out of the plane of the pyrimidine ring. MD and QM/MM computations of the enzyme-substrate (ES) complex also show the bond between the carboxylate group and the pyrimidine ring to be distorted with the distortion contributing a 10–15% decrease of the ΔΔG‡ value. These results are consistent with ODCase using both substrate distortion as well as transition state stabilization, primarily exerted by K72, in its catalysis of the OMP decarboxylation reaction.
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DOI：
10.1073/pnas.90.18.8600
发表时间：
1993-09-15
影响因子：
11.1
作者：
CHOOK, YM;KE, HM;LIPSCOMB, WN
通讯作者：
LIPSCOMB, WN
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
6.8
作者：
Gao, JL
通讯作者：
Gao, JL
影响因子：
2.9
作者：
Amyes TL;Richard JP
通讯作者：
Richard JP
DOI：
10.1107/s0907444994003112
发表时间：
1994-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
BAILEY, S
通讯作者：
BAILEY, S