Oxygen-insensitive nitroreductase E. coli NfsA, but not NfsB, is inhibited by fumarate.

Autor: Day MA; School of Biosciences, University of Birmingham, Birmingham, UK.; Institute for Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK., Jarrom D; School of Biosciences, University of Birmingham, Birmingham, UK., Rajah N; School of Biosciences, University of Birmingham, Birmingham, UK., Searle PF; Institute for Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK., Hyde EI; School of Biosciences, University of Birmingham, Birmingham, UK., White SA; School of Biosciences, University of Birmingham, Birmingham, UK.
Jazyk: angličtina
Zdroj: Proteins [Proteins] 2023 May; Vol. 91 (5), pp. 585-592. Date of Electronic Publication: 2022 Dec 13.
DOI: 10.1002/prot.26451
Abstrakt: Escherichia coli NfsA and NfsB are founding members of two flavoprotein families that catalyze the oxygen-insensitive reduction of nitroaromatics and quinones by NAD(P)H. This reduction is required for the activity of nitrofuran antibiotics and the enzymes have also been proposed for use with nitroaromatic prodrugs in cancer gene therapy and biocatalysis, but the roles of the proteins in vivo in bacteria are not known. NfsA is NADPH-specific whereas NfsB can also use NADH. The crystal structures of E. coli NfsA and NfsB and several analogs have been determined previously. In our crystal trials, we unexpectedly observed NfsA bound to fumarate. We here present the X-ray structure of the E. coli NfsA-fumarate complex and show that fumarate acts as a weak inhibitor of NfsA but not of NfsB. The structural basis of this differential inhibition is conserved in the two protein families and occurs at fumarate concentrations found in vivo, so impacting the efficacy of these proteins.
(© 2022 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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