3x21
Crystal structure of Escherichia coli nitroreductase NfsB mutant T41L/N71S/F124W
Structural highlights
FunctionNFSB_ECOLI Reduction of a variety of nitroaromatic compounds using NADH (and to lesser extent NADPH) as source of reducing equivalents; two electrons are transferred. Capable of reducing nitrofurazone, quinones and the anti-tumor agent CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide). The reduction of CB1954 results in the generation of cytotoxic species.[1] Publication Abstract from PubMedNitroreductases have great potential for the highly efficient reduction of aryl nitro compounds to arylhydroxylamines. However, regioselective reduction of the desired nitro group in polynitroarenes is still a challenge. Here, we describe the structure-based engineering of Escherichia coli nitroreductase NfsB to alter its regioselectivity, in order to achieve reduction of a target nitro group. When 2,4-dinitrotoluene was used as the substrate, the wild-type enzyme regioselectively reduced the 4-NO2 group, but the T41L/N71S/F124W mutant primarily reduced the 2-NO2 group, without loss of activity. The crystal structure of T41L/N71S/F124W and docking experiments indicated that the regioselectivity change (from 4-NO2 to 2-NO2 ) might result from the increased hydrophobicity of residues 41 and 124 (proximal to FMN) and conformational changes in residues 70 and 124. Altering the regioselectivity of a nitroreductase in the synthesis of arylhydroxylamines by structure-based engineering.,Bai J, Zhou Y, Chen Q, Yang Q, Yang J Chembiochem. 2015 May 26;16(8):1219-25. doi: 10.1002/cbic.201500070. Epub 2015, Apr 27. PMID:25917861[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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