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Mechanism-Guided Di...
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Kürten, CharlotteKTH,Proteomik och nanobioteknologi
(författare)
Mechanism-Guided Discovery of an Esterase Scaffold with Promiscuous Amidase Activity
- Artikel/kapitelEngelska2016
Förlag, utgivningsår, omfång ...
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2016-06-18
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MDPI AG,2016
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:kth-189936
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-189936URI
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https://doi.org/10.3390/catal6060090DOI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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QC 20160728
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The discovery and generation of biocatalysts with extended catalytic versatilities are of immense relevance in both chemistry and biotechnology. An enhanced atomistic understanding of enzyme promiscuity, a mechanism through which living systems acquire novel catalytic functions and specificities by evolution, would thus be of central interest. Using esterase-catalyzed amide bond hydrolysis as a model system, we pursued a simplistic in silico discovery program aiming for the identification of enzymes with an internal backbone hydrogen bond acceptor that could act as a reaction specificity shifter in hydrolytic enzymes. Focusing on stabilization of the rate limiting transition state of nitrogen inversion, our mechanism-guided approach predicted that the acyl hydrolase patatin of the alpha/beta phospholipase fold would display reaction promiscuity. Experimental analysis confirmed previously unknown high amidase over esterase activity displayed by the first described esterase machinery with a protein backbone hydrogen bond acceptor to the reacting NH-group of amides. The present work highlights the importance of a fundamental understanding of enzymatic reactions and its potential for predicting enzyme scaffolds displaying alternative chemistries amenable to further evolution by enzyme engineering.
Ämnesord och genrebeteckningar
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enzyme promiscuity
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enzyme catalysis
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biocatalysis
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reaction mechanisms
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molecular modeling
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amidase
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esterase
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Carlberg, BengtKTH,Proteomik och nanobioteknologi(Swepub:kth)u1d8t9q5
(författare)
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Syren, Per-OlofKTH,Proteomik och nanobioteknologi(Swepub:kth)u1ewlo1g
(författare)
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KTHProteomik och nanobioteknologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Catalysts: MDPI AG6:62073-4344
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