7q0o
From Proteopedia
E. coli NfsA
Structural highlights
FunctionNFSA_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 PubMedNitroreductases 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 AlsoReferences
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Categories: Escherichia coli K-12 | Large Structures | Day MA | Grainger A | Graziano A | Hyde EI | Jarrom D | Parr R | Searle PF | White SA
