Structural highlights
Function
NFSA_ECOLI Reduction of nitroaromatic compounds using NADH. Reduces nitrofurazone by a ping-pong bi-bi mechanism possibly to generate a two-electron transfer product. Major component of the oxygen-insensitive nitroreductase activity in E.coli.
Publication Abstract from PubMed
Nitroreductases activate nitroaromatic antibiotics and cancer prodrugs to cytotoxic hydroxylamines and reduce quinones to quinols. Using steady-state and stopped-flow kinetics we show that the E. coli nitroreductase NfsA is 20-50 fold more active with NADPH than with NADH and that product release may be rate-limiting. The crystal structure of NfsA with NADP(+) shows that a mobile loop forms a phosphate-binding pocket. The nicotinamide ring and nicotinamide ribose are mobile, as confirmed in molecular dynamics (MD) simulations. We present a model of NADPH bound to NfsA. Only one NADP(+) is seen bound to the NfsA dimers, and MD simulations show that binding of a second NADP(H) cofactor is unfavourable, suggesting that NfsA and other members of this protein superfamily may have a half-of-sites mechanism.
The 3D-structure, kinetics and dynamics of the E. coli nitroreductase NfsA with NADP(+) provide glimpses of its catalytic mechanism.,White SA, Christofferson AJ, Grainger AI, Day MA, Jarrom D, Graziano AE, Searle PF, Hyde EI FEBS Lett. 2022 Jun 1. doi: 10.1002/1873-3468.14413. PMID:35648111[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ White SA, Christofferson AJ, Grainger AI, Day MA, Jarrom D, Graziano AE, Searle PF, Hyde EI. The 3D-structure, kinetics and dynamics of the E. coli nitroreductase NfsA with NADP(+) provide glimpses of its catalytic mechanism. FEBS Lett. 2022 Jun 1. doi: 10.1002/1873-3468.14413. PMID:35648111 doi:http://dx.doi.org/10.1002/1873-3468.14413
