A mechanochemical switch to control radical intermediates.

Abstract:

:B₁₂-dependent enzymes employ radical species with exceptional prowess to catalyze some of the most chemically challenging, thermodynamically unfavorable reactions. However, dealing with highly reactive intermediates is an extremely demanding task, requiring sophisticated control strategies to prevent unwanted side reactions. Using hybrid quantum mechanical/molecular mechanical simulations, we follow the full catalytic cycle of an AdoB₁₂-dependent enzyme and present the details of a mechanism that utilizes a highly effective mechanochemical switch. When the switch is "off", the 5'-deoxyadenosyl radical moiety is stabilized by releasing the internal strain of an enzyme-imposed conformation. Turning the switch "on," the enzyme environment becomes the driving force to impose a distinct conformation of the 5'-deoxyadenosyl radical to avoid deleterious radical transfer. This mechanochemical switch illustrates the elaborate way in which enzymes attain selectivity of extremely chemically challenging reactions.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Brunk E,Kellett WF,Richards NG,Rothlisberger U

doi

10.1021/bi500050k

subject

Has Abstract

pub_date

2014-06-17 00:00:00

pages

3830-8

issue

23

eissn

0006-2960

issn

1520-4995

journal_volume

53

pub_type

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