Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Heavy enzymes and the rational redesign of protein catalysts

Allemann, Rudolf K ORCID: https://orcid.org/0000-0002-1323-8830, Scott, Alan F., Luk, Louis Y.-P. ORCID: https://orcid.org/0000-0002-7864-6261, Tuñón, Iñaki and Moliner, Vicent 2019. Heavy enzymes and the rational redesign of protein catalysts. ChemBioChem 20 (22) , pp. 2807-2812. 10.1002/cbic.201900134

[thumbnail of Scott_et_al-2019-ChemBioChem.pdf]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (771kB) | Preview
License URL: http://creativecommons.org/licenses/by/4.0
License Start date: 24 April 2019

Abstract

An unsolved mystery in biology concerns the link between enzyme catalysis and protein motions. Comparison between isotopically labelled “heavy” dihydrofolate reductases and their natural abundance counterparts has suggested that the coupling of protein motions to the chemistry of the catalysed reaction is minimized for hydride transfer. In alcohol dehydrogenase, non‐natural, bulky substrates that induce additional electrostatic rearrangements of the active site enhance coupled motions. This finding may provide a novel route engineer enzymes with altered substrate specificity, because amino acid residues responsible for dynamic coupling with a given substrate present as “hot spots” for mutagenesis. The routine engineering of enzymes to catalyse reactions of choice may eventually be possible through a detailed understanding of the biophysics of enzyme catalysis from insights gained from the analysis of “heavy” enzymes.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Publisher: Wiley
ISSN: 1439-4227
Funders: BBSRC
Date of First Compliant Deposit: 25 April 2019
Date of Acceptance: 18 April 2019
Last Modified: 08 May 2023 22:47
URI: https://orca.cardiff.ac.uk/id/eprint/121930

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics