Structure-Guided Discovery of N⁵-CAIR Mutase Inhibitors.

ABSTRACT: Because purine nucleotides are essential for all life, differences between how microbes and humans metabolize purines can be exploited for the development of antimicrobial therapies. While humans biosynthesize purine nucleotides in a 10-step pathway, most microbes utilize an additional 11th enzymatic activity. The human enzyme, aminoimidazole ribonucleotide (AIR) carboxylase generates the product 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) directly. Most microbes, however, require two separate enzymes, a synthetase (PurK) and a mutase (PurE), and proceed through the intermediate, N⁵-CAIR. Toward the development of therapeutics that target these differences, we have solved crystal structures of the N⁵-CAIR mutase of the human pathogens Legionella pneumophila

SUBMITTER: Belfon KKJ 

PROVIDER: S-EPMC10484210 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature