Direct Participation of a Peripheral Side Chain of a Corrin Ring in Coenzyme B12 Catalysis.
Direct Participation of a Peripheral Side Chain of a Corrin Ring in Coenzyme B12 Catalysis.
复制标题
Corrin 环的外围侧链直接参与辅酶 B12 催化。
作者：
N. Shibata;Y. Sueyoshi;Y. Higuchi;T. Toraya
B12依赖性异构酶（消除）二醇脱氢酶和乙醇胺氨裂解酶与腺苷钴胺素复合的晶体结构在有和没有底物的情况下得到解决。结构表明，咕啉环的外围α-乙酰胺侧链直接与腺苷基团相互作用，以保持该基团处于催化位置，并且该侧链以与辅酶和底物/产物之间的自由基穿梭同步的方式在原始位置和催化位置之间摆动。涉及直接或间接通过与α-侧链相互作用协同参与腺苷基定位的关键残基的突变降低了周转率并增加了由不期望的副反应引起的不可逆失活的相对速率。这些发现指导了酶的工程设计，以改善催化作用，并通过利用自由基物种的高反应性来生产有用的化学品。
The crystal structures of the B12 -dependent isomerases (eliminating) diol dehydratase and ethanolamine ammonia-lyase complexed with adenosylcobalamin were solved with and without substrates. The structures revealed that the peripheral a-acetamide side chain of the corrin ring directly interacts with the adenosyl group to maintain the group in the catalytic position, and that this side chain swings between the original and catalytic positions in a synchronized manner with the radical shuttling between the coenzyme and substrate/product. Mutations involving key residues that cooperatively participate in the positioning of the adenosyl group, directly or indirectly through the interaction with the a-side chain, decreased the turnover rate and increased the relative rate of irreversible inactivation caused by undesirable side reactions. These findings guide the engineering of enzymes for improved catalysis and producing useful chemicals by utilizing the high reactivity of radical species.
影响因子：
56.9
作者：
DRENNAN, CL;HUANG, S;LUDWIG, ML
通讯作者：
LUDWIG, ML
蛋白质如何准备 B12 结合：破伤风梭菌谷氨酸变位酶 B12 结合亚基的结构和动力学。
DOI：
10.1016/s0969-2126(98)00103-8
发表时间：
1998
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Tollinger,M;Konrat,R;Hilbert,BH;Marsh,EN;Kräutler,B
通讯作者：
Kräutler,B
DOI：
10.1073/pnas.0407074101
发表时间：
2004-11-09
影响因子：
11.1
作者：
Berkovitch, F;Behshad, E;Drennan, CL
通讯作者：
Drennan, CL