Screening a knowledge-based library of low molecular weight compounds against the proline biosynthetic enzyme 1-pyrroline-5-carboxylate 1 (PYCR1).

ABSTRACT: Δ¹-pyrroline-5-carboxylate reductase isoform 1 (PYCR1) is the last enzyme of proline biosynthesis and catalyzes the NAD(P)H-dependent reduction of Δ¹-pyrroline-5-carboxylate to L-proline. High PYCR1 gene expression is observed in many cancers and linked to poor patient outcomes and tumor aggressiveness. The knockdown of the PYCR1 gene or the inhibition of PYCR1 enzyme has been shown to inhibit tumorigenesis in cancer cells and animal models of cancer, motivating inhibitor discovery. We screened a library of 71 low molecular weight compounds (average MW of 131 Da) against PYCR1 using an enzyme activity assay. Hit compounds were validated with X-ray crystallography and kinetic assays to determine affinity parameters. The library was counter-screened against human Δ

SUBMITTER: Meeks KR 

PROVIDER: S-EPMC11193152 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature