Search: WFRF:(Syrén Per Olof) >
Mechanism-Guided Di...
-
Kürten, CharlotteKTH,Proteomik och nanobioteknologi
(author)
Mechanism-Guided Discovery of an Esterase Scaffold with Promiscuous Amidase Activity
- Article/chapterEnglish2016
Publisher, publication year, extent ...
-
2016-06-18
-
MDPI AG,2016
-
printrdacarrier
Numbers
-
LIBRIS-ID:oai:DiVA.org:kth-189936
-
https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-189936URI
-
https://doi.org/10.3390/catal6060090DOI
Supplementary language notes
-
Language:English
-
Summary in:English
Part of subdatabase
Classification
-
Subject category:ref swepub-contenttype
-
Subject category:art swepub-publicationtype
Notes
-
QC 20160728
-
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.
Subject headings and genre
-
enzyme promiscuity
-
enzyme catalysis
-
biocatalysis
-
reaction mechanisms
-
molecular modeling
-
amidase
-
esterase
Added entries (persons, corporate bodies, meetings, titles ...)
-
Carlberg, BengtKTH,Proteomik och nanobioteknologi(Swepub:kth)u1d8t9q5
(author)
-
Syren, Per-OlofKTH,Proteomik och nanobioteknologi(Swepub:kth)u1ewlo1g
(author)
-
KTHProteomik och nanobioteknologi
(creator_code:org_t)
Related titles
-
In:Catalysts: MDPI AG6:62073-4344
Internet link
Find in a library
-
Catalysts
(Search for host publication in LIBRIS)
To the university's database