Repair processes in the metabolism as drugs targets
November 2022
University of Wuerzburg, Wuerzburg, Germany
Repair enzymes may represent an alternative target class for selective metabolic inhibition, e.g. for cancer treatment, but pharmacological tools to test this concept are still needed.
In this study, it was demonstrated that phosphoglycolate phosphatase (PGP), a repair enzyme in glycolysis, can be targeted with a small molecular compound. Using a combination of small molecule screening, protein crystallography, molecular dynamics simulations and NMR metabolomics, a compound was identified that inhibits PGP with high selectivity by locking the phosphatase in an inactive conformation. The compound was characterized by biochemical and cellular assays.
This study provides key insights into effective PGP targeting, thereby offering an approach to control glycolysis, and at the same time demonstrates the feasibility of therapeutic approaches to target cellular metabolism.
Glycolytic flux control by drugging phosphoglycolate phosphatase
Antje Gohla
Added on: 11-21-2022
[1] https://www.nature.com/articles/s41467-022-34228-2
