Water Promoting Electron Hole Transport between Tyrosine and Cysteine in Proteins via a Special Mechanism: Double Proton Coupled Electron Transfer

摘要

The proton/electron transfer reactions between cysteine residue (Cys) and tyrosinyl radical (Tyr~·) are an important step for many enzyme-catalyzed processes. On the basis of the statistical analysis of protein data bank, we designed three representative models to explore the possible proton/ electron transfer mechanisms from Cys to Tyr~· in proteins. Our ab initio calculations on simplified models and quantum mechanical/molecular mechanical (QM/MM) calculations on real protein environment reveal that the direct electron transfer between Cys and Tyr~· is difficult to occur, but an inserted water molecule can greatly promote the proton/electron transfer reactions by a double-proton-coupled electron transfer (dPCET) mechanism. The inserted H_2O plays two assistant roles in these reactions. The first one is to bridge the side chains of Tyr~· and Cys via two hydrogen bonds, which act as the proton pathway, and the other one is to enhance the electron overlap between the lone-pair orbital of sulfur atom and the π-orbital of phenol moiety and to function as electron transfer pathway. This water-mediated dPCET mechanism may offer great help to understand the detailed electron transfer processes between Tyr and Cys residues in proteins, such as the electron transfer from Cys_(439) to Tyr_(730)~· in the class Ⅰ ribonucleotide reductase.