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| | ==Crystal structure of Escherichia coli nitroreductase NfsB mutant T41L/N71S/F124W== | | ==Crystal structure of Escherichia coli nitroreductase NfsB mutant T41L/N71S/F124W== |
| - | <StructureSection load='3x21' size='340' side='right' caption='[[3x21]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='3x21' size='340' side='right'caption='[[3x21]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3x21]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3X21 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3X21 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3x21]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3X21 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3X21 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.002Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ds7|1ds7]], [[3x22|3x22]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">nfnB, dprA, nfsB, nfsI, ntr ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3x21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3x21 OCA], [https://pdbe.org/3x21 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3x21 RCSB], [https://www.ebi.ac.uk/pdbsum/3x21 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3x21 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/6,7-dihydropteridine_reductase 6,7-dihydropteridine reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.34 1.5.1.34] </span></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3x21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3x21 OCA], [http://pdbe.org/3x21 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3x21 RCSB], [http://www.ebi.ac.uk/pdbsum/3x21 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3x21 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NFNB_ECOLI NFNB_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.<ref>PMID:15684426</ref> | + | [https://www.uniprot.org/uniprot/NFSB_ECOLI NFSB_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.<ref>PMID:15684426</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Nitroreductase|Nitroreductase]] | + | *[[Nitroreductase 3D structures|Nitroreductase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 6,7-dihydropteridine reductase]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Ecoli]] | + | [[Category: Large Structures]] |
| - | [[Category: Bai, J]] | + | [[Category: Bai J]] |
| - | [[Category: Yang, J]] | + | [[Category: Yang J]] |
| - | [[Category: Yang, Q]] | + | [[Category: Yang Q]] |
| - | [[Category: Zhou, Y]] | + | [[Category: Zhou Y]] |
| - | [[Category: Dinitrocompound]]
| + | |
| - | [[Category: Nitroreductase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Regioselectivity]]
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| Structural highlights
Function
NFSB_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 PubMed
Nitroreductases 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 Also
References
- ↑ Race PR, Lovering AL, Green RM, Ossor A, White SA, Searle PF, Wrighton CJ, Hyde EI. Structural and mechanistic studies of Escherichia coli nitroreductase with the antibiotic nitrofurazone. Reversed binding orientations in different redox states of the enzyme. J Biol Chem. 2005 Apr 8;280(14):13256-64. Epub 2005 Jan 31. PMID:15684426 doi:http://dx.doi.org/10.1074/jbc.M409652200
- ↑ Bai J, Zhou Y, Chen Q, Yang Q, Yang J. Altering the regioselectivity of a nitroreductase in the synthesis of arylhydroxylamines by structure-based engineering. Chembiochem. 2015 May 26;16(8):1219-25. doi: 10.1002/cbic.201500070. Epub 2015, Apr 27. PMID:25917861 doi:http://dx.doi.org/10.1002/cbic.201500070
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