X-ray-driven chemistry and conformational heterogeneity in atomic resolution crystal structures of bacterial dihydrofolate reductases.

ABSTRACT: Dihydrofolate reductase (DHFR) catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate. Bacterial DHFRs are targets of several important antibiotics as well as model enzymes for the role of protein conformational dynamics in enzyme catalysis. We collected 0.93 Å resolution X-ray diffraction data from both Bacillus subtilis (Bs) and E. coli (Ec) DHFRs bound to folate and NADP⁺. These oxidized ternary complexes should not be able to perform chemistry, however electron density maps suggest hydride transfer is occurring in both enzymes. Comparison of low- and high-dose EcDHFR datasets show that X-rays drive partial production of tetrahydrofolate. Hydride transfer causes the nicotinamide moiety of NADP⁺ to move towards the folate as well

SUBMITTER: Smith N 

PROVIDER: S-EPMC10659368 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature