ArticleStructure (London, England : 1993)2017
Mechanism-Informed Refinement Reveals Altered Substrate-Binding Mode for Catalytically Competent Nitroreductase.
Article in Structure (London, England : 1993), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- Kinetic characterization of the C-terminal domain of Malonyl-CoA reductase.Biochimica et biophysica acta. Proteins and proteomics · 2024Article
- Structural Evaluation of a Nitroreductase Engineered for Improved Activation of the 5-Nitroimidazole PET Probe SN33623.International journal of molecular sciences · 2024Article
- Oxygen-insensitive nitroreductase E. coli NfsA, but not NfsB, is inhibited by fumarate.Proteins · 2023Article
- Substrate Electronics Dominate the Rate of Reductive Dehalogenation Promoted by the Flavin-Dependent Iodotyrosine Deiodinase.Biochemistry · 2023Article
- Structure and Dynamics of ThreeInternational journal of molecular sciences · 2023Article
- The 3D-structure, kinetics and dynamics of the E. coli nitroreductase NfsA with NADPFEBS letters · 2022Article
- Dark Dynamic Therapy: Photosensitization without Light Excitation Using Chemiluminescence Resonance Energy Transfer in a Dioxetane-Erythrosin B Conjugate.ACS chemical biology · 2022Article
- Functional and Structural Characterization of Diverse NfsB Chloramphenicol Reductase Enzymes from Human Pathogens.Microbiology spectrum · 2022Article
- Sequence Conservation Does Not Always Signify a Functional Imperative as Observed in the Nitroreductase Superfamily.Biochemistry · 2022Article
- Versatile selective evolutionary pressure using synthetic defect in universal metabolism.Nature communications · 2021Article
- The structures of E. coli NfsA bound to the antibiotic nitrofurantoin; to 1,4-benzoquinone and to FMN.The Biochemical journal · 2021Article
- Asymmetric ligand binding in homodimeric Enterobacter cloacae nitroreductase yields the Michaelis complex for nitroaromatic substrates.Journal of molecular modeling · 2020Article
- Degradation of High Energy Materials Using Biological Reduction: A Rational Way to Reach Bioremediation.International journal of molecular sciences · 2019Article
- Informing Efforts to Develop Nitroreductase for Amine Production.Molecules (Basel, Switzerland) · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Nitroreductase (NR) from Enterobacter cloacae reduces diverse nitroaromatics including herbicides, explosives, and prodrugs, and holds promise for bioremediation, prodrug activation, and enzyme-assisted synthesis. We solved crystal structures of NR complexes with bound substrate or analog for each of its two half-reactions. We complemented these with kinetic isotope effect (KIE) measurements elucidating H-transfer steps essential to each half-reaction. KIEs indicate hydride transfer from NADH to the flavin consistent with our structure of NR with the NADH analog nicotinic acid adenine dinucleotide (NAAD). The KIE on reduction of p-nitrobenzoic acid (p-NBA) also indicates hydride transfer, and requires revision of prior computational mechanisms. Our mechanistic information provided a structural restraint for the orientation of bound substrate, placing the nitro group closer to the flavin N5 in the pocket that binds the amide of NADH. KIEs show that solvent provides a proton, enabling accommodation of different nitro group placements, consistent with the broad repertoire of NR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.