A Mechanochemical Switch to Control Radical Intermediates

dc.contributor.authorBrunk, Elizabeth
dc.contributor.authorKellett, Whitney F.
dc.contributor.authorRichards, Nigel G. J.
dc.contributor.authorRothlisberger, Ursula
dc.contributor.departmentDepartment of Chemistry & Chemical Biology, School of Scienceen_US
dc.date.accessioned2016-02-23T16:58:01Z
dc.date.available2016-02-23T16:58:01Z
dc.date.issued2014-06-17
dc.description.abstractB12-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.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationBrunk, E., Kellett, W. F., Richards, N. G. J., & Rothlisberger, U. (2014). A Mechanochemical Switch to Control Radical Intermediates. Biochemistry, 53(23), 3830–3838. http://doi.org/10.1021/bi500050ken_US
dc.identifier.issn0006-2960en_US
dc.identifier.urihttps://hdl.handle.net/1805/8434
dc.language.isoen_USen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.isversionof10.1021/bi500050ken_US
dc.relation.journalBiochemistryen_US
dc.rightsIUPUI Open Access Policyen_US
dc.sourcePublisheren_US
dc.subjectAcyl Coenzyme Aen_US
dc.subjectmetabolismen_US
dc.subjectBacterial Proteinsen_US
dc.subjectCobamidesen_US
dc.subjectFree Radicalsen_US
dc.subjectantagonists & inhibitorsen_US
dc.subjectMethylmalonyl-CoA Mutaseen_US
dc.subjectModels, Molecularen_US
dc.titleA Mechanochemical Switch to Control Radical Intermediatesen_US
dc.typeArticleen_US
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