Charge Separation Propensity of the Coenzyme B12鈥揟yrosine Complex in Adenosylcobalamin-Dependent Methylmalonyl鈥揅oA Mutase Enzyme

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• 作者：Neeraj Kumar ; Shubin Liu ; Pawel M. Kozlowski
• 刊名：The Journal of Physical Chemistry Letters
• 出版年：2012
• 出版时间：April 19, 2012
• 年：2012
• 卷：3
• 期：8
• 页码：1035-1038
• 全文大小：275K
• 年卷期：v.3,no.8(April 19, 2012)
• ISSN：1948-7185

文摘

We report the electrophilic Fukui function analysis based on density functional reactivity theory (DFRT) to demonstrate the feasibility of the proton-coupled electron transfer (PCET) mechanism. To characterize the charge propensity of an electron-transfer site other than the proton-acceptor site of the coenzyme B₁₂鈥搕yrosine complex, several structural models (ranging from minimal to actual enzyme scaffolds) have been employed at DFT and QM/MM computations. It is shown, based on the methylmalonyl-CoA mutase (MCM) enzyme that substrate binding plays a significant role in displacing the phenoxyl proton of the tyrosine (Y89), which initiates the electron transfer from Y89 to coenzyme B₁₂. PCET-based enzymatic reaction implies that one electron-reduced form of the AdoCbl cofactor induces the cleavage of the Co鈥揅 bond, as an alternative to its neutral analogue, which can assist in understanding the origin of the observed trillion-fold rate enhancement in MCM enzyme.

Keywords:

density functional reactivity theory; proton-coupled electron transfer; coenzyme B₁₂鈭抰yrosine complex; enzymes