Evidence map›Paper›PMID 28578873›Full record

ArticleStructure (London, England : 1993)2017

Mechanism-Informed Refinement Reveals Altered Substrate-Binding Mode for Catalytically Competent Nitroreductase.

Warintra Pitsawong, Chad A Haynes, Ronald L Koder, David W Rodgers, Anne-Frances Miller

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.7field-weighted citation impact, top 39% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 30 citations in OpenAlex.

  1. Kinetic characterization of the C-terminal domain of Malonyl-CoA reductase.Biochimica et biophysica acta. Proteins and proteomics · 2024
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  5. Structure and Dynamics of ThreeInternational journal of molecular sciences · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Warintra PitsawongDepartment of Chemistry, University of Kentucky, 505 Rose Street, Lexington, KY 40506-0055, USA.
Chad A HaynesDepartment of Molecular and Cellular Biochemistry and Center for Structural Biology, University of Kentucky, 741 South Limestone Street, Lexington, KY 40536-0509, USA.
Ronald L KoderDepartment of Chemistry, University of Kentucky, 505 Rose Street, Lexington, KY 40506-0055, USA.
David W RodgersDepartment of Molecular and Cellular Biochemistry and Center for Structural Biology, University of Kentucky, 741 South Limestone Street, Lexington, KY 40536-0509, USA. Electronic address: david.rodgers@uky.edu.
Anne-Frances MillerDepartment of Chemistry, University of Kentucky, 505 Rose Street, Lexington, KY 40506-0055, USA; Department of Molecular and Cellular Biochemistry and Center for Structural Biology, University of Kentucky, 741 South Limestone Street, Lexington, KY 40536-0509, USA. Electronic address: afmill3r2@gmail.com.
University of Kentucky · US

Funding

Protein CoreP30GM110787 · NIGMS · UNIVERSITY OF KENTUCKY · PI MENDENHALL, MICHAEL D. · 2014 to 2018
$5.7M
BioCARS: A Synchrotron Structure Biology ResourceR24GM111072 · NIGMS · UNIVERSITY OF CHICAGO · PI MOFFAT, JOHN KEITH · 2013 to 2016
$2.3M
Neuropeptidase FunctionR01NS038041 · NINDS · UNIVERSITY OF KENTUCKY · PI RODGERS, DAVID W · 2001 to 2004
$1.0M
Neuropeptidase FunctionR56NS038041 · NINDS · UNIVERSITY OF KENTUCKY · PI RODGERS, DAVID W · 2007 to 2007
$330k
Nitroreductase: Determinants of Flavin Enzyme ActivityR01GM063921 · NIGMS · UNIVERSITY OF KENTUCKY · PI MILLER, ANNE-FRANCES · 2003 to 2004
$209k
NIGMS NIH HHS P30 GM110787NIGMS NIH HHS R01 GM063921NIGMS NIH HHS R24 GM111072NINDS NIH HHS R01 NS038041NINDS NIH HHS R56 NS038041
6 · The paper itself

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.

Indexed as

Bacterial ProteinsBinding SitesEnterobacter cloacaeFlavinsNADNitrobenzoatesNitroreductasesProtein BindingSubstrate SpecificityBacterial ProteinsFlavinsNADNitrobenzoatesNitroreductasesflavoenzymeisotope effectsnitroreductaseprodrug activationremediationstructuresubstrate binding mode

Identifiers

PMID28578873
PMCPMC5560098
OpenAlexW2621273735

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.