Orotidine 5鈥?Monophosphate Decarboxylase: Transition State Stabilization from Remote Protein鈥揚hosphodianion Interactions

详细信息    查看全文

• 作者：Tina L. Amyes ; Shonoi A. Ming ; Lawrence M. Goldman ; B. McKay Wood ; Bijoy J. Desai ; John A. Gerlt ; John P. Richard
• 刊名：Biochemistry
• 出版年：2012
• 出版时间：June 12, 2012
• 年：2012
• 卷：51
• 期：23
• 页码：4630-4632
• 全文大小：203K
• 年卷期：v.51,no.23(June 12, 2012)
• ISSN：1520-4995

文摘

Mutants of orotidine 5鈥?monophosphate decarboxylase containing all possible single (Q215A, Y217F, and R235A), double, and triple substitutions of the side chains that interact with the phosphodianion group of the substrate orotidine 5鈥?monophosphate have been prepared. Essentially the entire effect of these mutations on the decarboxylation of the truncated neutral substrate 1-(尾-an class="smallcaps">dan>-erythrofuranosyl)orotic acid that lacks a phosphodianion group is expressed as a decrease in the third-order rate constant for activation by phosphite dianion. The results are consistent with a model in which phosphodianion binding interactions are utilized to stabilize a rare closed enzyme form that exhibits a high catalytic activity for decarboxylation.