Methyltransferases do not work by compression, cratic, or desolvation effects, but by electrostatic preorganization. Issue 2 (7th January 2015)

• Record Type: Journal Article
• Authors: Lameira, Jeronimo; Bora, Ram Prasad; Chu, Zhen T.; Warshel, Arieh
• Is Part Of: Proteins. Volume 83:Issue 2(2015)
• Page Start: 318
• Page End: 330
• Publication Date: 2015-01-07
• Subjects: methyltransferase -- compression -- NAC -- electrostatic -- preorganization; Proteins -- Periodicals; Proteins -- Periodicals; 572.6
• DOI: 10.1002/prot.24717
• Languages: English
• ISSNs: 0887-3585

Abstract

ABSTRACT: The enzyme catechol O ‐methyltransferase (COMT) catalyzes the transfer of a methyl group from S ‐adenosylmethionine to dopamine and related catechols. The search for the origin of COMT catalysis has led to different proposals and hypothesis, including the entropic, the NAC, and the compression proposals as well as the more reasonable electrostatic idea. Thus, it is important to understand the catalytic power of this enzyme and to examine the validity of different proposals and in particular the repeated recent implication of the compression idea. The corresponding analysis should be done by well‐defined physically‐based considerations that involve computations rather than circular interpretations of experimental results. Thus, we explore here the origin of the catalytic efficiency of COMT by using the empirical valence bond and the linear response approximation approaches. The results demonstrate that the catalytic effect of COMT is mainly due to electrostatic preorganization effects. It is also shown that the compression, NAC and entropic proposals do not account for the catalytic effect. Proteins 2015; 83:318–330. © 2014 Wiley Periodicals, Inc.