Full metadata record
DC FieldValueLanguage
dc.contributor.authorBlomberg, Rebecca-
dc.contributor.authorKries, Hajo-
dc.contributor.authorPinkas, Daniel M.-
dc.contributor.authorMittl, Peer R. E.-
dc.contributor.authorGrütter, Markus G.-
dc.contributor.authorPrivett, Heidi K.-
dc.contributor.authorMayo, Stephen L.-
dc.contributor.authorHilvert, Donald-
dc.date.accessioned2018-08-24T14:25:33Z-
dc.date.available2018-08-24T14:25:33Z-
dc.date.issued2013-
dc.identifier.issn0028-0836de_CH
dc.identifier.issn1476-4687de_CH
dc.identifier.urihttps://digitalcollection.zhaw.ch/handle/11475/9661-
dc.description.abstractLinus Pauling established the conceptual framework for understanding and mimicking enzymes more than six decades ago. The notion that enzymes selectively stabilize the rate-limiting transition state of the catalysed reaction relative to the bound ground state reduces the problem of design to one of molecular recognition. Nevertheless, past attempts to capitalize on this idea, for example by using transition state analogues to elicit antibodies with catalytic activities, have generally failed to deliver true enzymatic rates. The advent of computational design approaches, combined with directed evolution, has provided an opportunity to revisit this problem. Starting from a computationally designed catalyst for the Kemp elimination--a well-studied model system for proton transfer from carbon – we show that an artificial enzyme can be evolved that accelerates an elementary chemical reaction 6 × 10(8)-fold, approaching the exceptional efficiency of highly optimized natural enzymes such as triosephosphate isomerase. A 1.09 Å resolution crystal structure of the evolved enzyme indicates that familiar catalytic strategies such as shape complementarity and precisely placed catalytic groups can be successfully harnessed to afford such high rate accelerations, making us optimistic about the prospects of designing more sophisticated catalysts.de_CH
dc.language.isoende_CH
dc.publisherSpringerde_CH
dc.relation.ispartofNaturede_CH
dc.rightsLicence according to publishing contractde_CH
dc.subjectCarbonde_CH
dc.subjectCatalytic domainde_CH
dc.subjectX-ray crystallographyde_CH
dc.subjectEnzymesde_CH
dc.subjectKineticsde_CH
dc.subjectMolecular modelsde_CH
dc.subjectProtonsde_CH
dc.subjectTriazolesde_CH
dc.subjectTriose-phosphate isomerasede_CH
dc.subjectBiocatalysisde_CH
dc.subjectDirected molecular evolutionde_CH
dc.subjectProtein engineeringde_CH
dc.subject.ddc660.6: Biotechnologiede_CH
dc.titlePrecision is essential for efficient catalysis in an evolved Kemp eliminasede_CH
dc.typeBeitrag in wissenschaftlicher Zeitschriftde_CH
dcterms.typeTextde_CH
zhaw.departementLife Sciences und Facility Managementde_CH
zhaw.organisationalunitInstitut für Chemie und Biotechnologie (ICBT)de_CH
dc.identifier.doi10.1038/nature12623de_CH
dc.identifier.pmid24132235de_CH
zhaw.funding.euNode_CH
zhaw.issue503de_CH
zhaw.originated.zhawNode_CH
zhaw.pages.end421de_CH
zhaw.pages.start418de_CH
zhaw.publication.statuspublishedVersionde_CH
zhaw.volume2013de_CH
zhaw.publication.reviewPeer review (Publikation)de_CH
zhaw.webfeedBiokatalysede_CH
Appears in collections:Publikationen Life Sciences und Facility Management

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.