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New page: left|200px<br /><applet load="1icv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1icv, resolution 2.4Å" /> '''THE STRUCTURE OF ESCH...
 
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[[Image:1icv.jpg|left|200px]]<br /><applet load="1icv" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1icv, resolution 2.4&Aring;" />
'''THE STRUCTURE OF ESCHERICHIA COLI NITROREDUCTASE COMPLEXED WITH NICOTINIC ACID'''<br />


==Overview==
==THE STRUCTURE OF ESCHERICHIA COLI NITROREDUCTASE COMPLEXED WITH NICOTINIC ACID==
Escherichia coli nitroreductase is a flavoprotein that reduces a variety, of quinone and nitroaromatic substrates. Its ability to convert relatively, non-toxic prodrugs such as CB1954 (5-[aziridin-1-yl]-2,4-dinitrobenzamide), into highly cytotoxic derivatives has led to interest in its potential for, cancer gene therapy. We have determined the structure of the enzyme bound, to a substrate analogue, nicotinic acid, from three crystal forms at, resolutions of 1.7 A, 1.8 A and 2.4 A, representing ten, non-crystallographically related monomers. The enzyme is dimeric, and has, a large hydrophobic core; each half of the molecule consists of a, five-stranded beta-sheet surrounded by alpha-helices. Helices F and F, protrude from the core region of each monomer. There is an extensive dimer, interface, and the 15 C-terminal residues extend around the opposing, monomer, contributing the fifth beta-strand. The active sites lie on, opposite sides of the molecule, in solvent-exposed clefts at the dimer, interface. The FMN forms hydrogen bonds to one monomer and hydrophobic, contacts to both; its si face is buried. The nicotinic acid stacks between, the re face of the FMN and Phe124 in helix F, with only one hydrogen bond, to the protein. If the nicotinamide ring of the coenzyme NAD(P)H were in, the same position as that of the nicotinic acid ligand, its C4 atom would, be optimally positioned for direct hydride transfer to flavin N5., Comparison of the structure with unliganded flavin reductase and NTR, suggests reduced mobility of helices E and F upon ligand binding. Analysis, of the structure explains the broad substrate specificity of the enzyme, and provides the basis for rational design of novel prodrugs and for, site-directed mutagenesis for improved enzyme activity.
<StructureSection load='1icv' size='340' side='right'caption='[[1icv]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1icv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ICV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ICV FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</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>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NIO:NICOTINIC+ACID'>NIO</scene></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=1icv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1icv OCA], [https://pdbe.org/1icv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1icv RCSB], [https://www.ebi.ac.uk/pdbsum/1icv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1icv ProSAT]</span></td></tr>
</table>
== Function ==
[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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ic/1icv_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1icv ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1ICV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with FMN and NIO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ICV OCA].
*[[Nitroreductase 3D structures|Nitroreductase 3D structures]]
 
== References ==
==Reference==
<references/>
The structure of Escherichia coli nitroreductase complexed with nicotinic acid: three crystal forms at 1.7 A, 1.8 A and 2.4 A resolution., Lovering AL, Hyde EI, Searle PF, White SA, J Mol Biol. 2001 May 25;309(1):203-13. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11491290 11491290]
__TOC__
[[Category: 6,7-dihydropteridine reductase]]
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Hyde, E.I.]]
[[Category: Hyde EI]]
[[Category: Lovering, A.L.]]
[[Category: Lovering AL]]
[[Category: Searle, P.F.]]
[[Category: Searle PF]]
[[Category: White, S.A.]]
[[Category: White SA]]
[[Category: FMN]]
[[Category: NIO]]
[[Category: alpha-beta]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 17:17:37 2007''

Latest revision as of 10:46, 3 April 2024

THE STRUCTURE OF ESCHERICHIA COLI NITROREDUCTASE COMPLEXED WITH NICOTINIC ACIDTHE STRUCTURE OF ESCHERICHIA COLI NITROREDUCTASE COMPLEXED WITH NICOTINIC ACID

Structural highlights

1icv is a 4 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.4Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ 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

1icv, resolution 2.40Å

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