Racemases and epimerases operating through a 1,1-proton transfer mechanism: reactivity, mechanism and inhibition.

Lloyd, Matthew D, Yevglevskis, Maksims, Nathubhai, Amit, James, Tony D, Threadgill, Michael D and Woodman, Timothy J (2021) Racemases and epimerases operating through a 1,1-proton transfer mechanism: reactivity, mechanism and inhibition. Chemical Society reviews, 50 (10). pp. 5952-5984. ISSN 1460-4744

13574.pdf - Published Version
Available under License Creative Commons Attribution.

Download (6MB) | Preview

Search Google Scholar


Racemases and epimerases catalyse changes in the stereochemical configurations of chiral centres and are of interest as model enzymes and as biotechnological tools. They also occupy pivotal positions within metabolic pathways and, hence, many of them are important drug targets. This review summarises the catalytic mechanisms of PLP-dependent, enolase family and cofactor-independent racemases and epimerases operating by a deprotonation/reprotonation (1,1-proton transfer) mechanism and methods for measuring their catalytic activity. Strategies for inhibiting these enzymes are reviewed, as are specific examples of inhibitors. Rational design of inhibitors based on substrates has been extensively explored but there is considerable scope for development of transition-state mimics and covalent inhibitors and for the identification of inhibitors by high-throughput, fragment and virtual screening approaches. The increasing availability of enzyme structures obtained using X-ray crystallography will facilitate development of inhibitors by rational design and fragment screening, whilst protein models will facilitate development of transition-state mimics.

Item Type: Article
Additional Information: ** From PubMed via Jisc Publications Router
Divisions: Faculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences
SWORD Depositor: Publication Router
Depositing User: Publication Router
Date Deposited: 22 Jun 2021 13:47
Last Modified: 22 Jun 2021 14:00
URI: http://sure.sunderland.ac.uk/id/eprint/13574
ORCID for Matthew D Lloyd: ORCID iD orcid.org/0000-0002-4821-4361
ORCID for Amit Nathubhai: ORCID iD orcid.org/0000-0003-3686-2799
ORCID for Tony D James: ORCID iD orcid.org/0000-0002-4095-2191

Actions (login required)

View Item View Item


Downloads per month over past year