A Mechanochemical Switch to Control Radical Intermediates

B-12-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 AdoB(12)-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.


Published in:
Biochemistry, 53, 23, 3830-3838
Year:
2014
Publisher:
Washington, American Chemical Society
ISSN:
0006-2960
Laboratories:




 Record created 2014-08-29, last modified 2018-09-13


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