|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of RdxA from Helicobacter pyroli== | | ==Crystal structure of RdxA from Helicobacter pyroli== |
| - | <StructureSection load='3qdl' size='340' side='right' caption='[[3qdl]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3qdl' size='340' side='right'caption='[[3qdl]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qdl]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_43504 Atcc 43504]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QDL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QDL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qdl]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_43504 Atcc 43504]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QDL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QDL 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>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </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=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">rdxA, HP_0954 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=210 ATCC 43504])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">rdxA, HP_0954 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=210 ATCC 43504])</td></tr> |
| - | <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=3qdl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qdl OCA], [http://pdbe.org/3qdl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qdl RCSB], [http://www.ebi.ac.uk/pdbsum/3qdl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qdl ProSAT]</span></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=3qdl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qdl OCA], [https://pdbe.org/3qdl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qdl RCSB], [https://www.ebi.ac.uk/pdbsum/3qdl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qdl ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RDXA_HELPY RDXA_HELPY]] Reduction of a variety of nitroaromatic compounds using NADPH as source of reducing equivalents; two electrons are transferred (By similarity). Capable of reducing metronidazole; inactive RdxA renders the bacterium resistant to this compound. The reduction of metronidazole generates hydroxylamine, a potent mutagen and bactericide.<ref>PMID:9622362</ref> | + | [[https://www.uniprot.org/uniprot/RDXA_HELPY RDXA_HELPY]] Reduction of a variety of nitroaromatic compounds using NADPH as source of reducing equivalents; two electrons are transferred (By similarity). Capable of reducing metronidazole; inactive RdxA renders the bacterium resistant to this compound. The reduction of metronidazole generates hydroxylamine, a potent mutagen and bactericide.<ref>PMID:9622362</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 27: |
Line 27: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Atcc 43504]] | | [[Category: Atcc 43504]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Hoffman, P S]] | | [[Category: Hoffman, P S]] |
| | [[Category: Martinez-Julvez, M]] | | [[Category: Martinez-Julvez, M]] |
| Structural highlights
Function
[RDXA_HELPY] Reduction of a variety of nitroaromatic compounds using NADPH as source of reducing equivalents; two electrons are transferred (By similarity). Capable of reducing metronidazole; inactive RdxA renders the bacterium resistant to this compound. The reduction of metronidazole generates hydroxylamine, a potent mutagen and bactericide.[1]
Publication Abstract from PubMed
The RdxA oxygen insensitive nitroreductase of the human gastric pathogen Helicobacter pylori is responsible for the susceptibility of this organism to the redox active prodrug metronidazole (MTZ). Loss-of-function mutations in rdxA are primarily responsible for resistance to this therapeutic. RdxA exhibits potent NADPH oxidase activity under aerobic conditions and metronidazole reductase activity under strictly anaerobic conditions. Here we report the crystal structure of RdxA, which is a homodimer exhibiting domain swapping and containing two molecules of FMN bound at the dimer interface. We have found a gap between the side chain of Tyr47 and the isoalloxazine ring of FMN that seems appropriate for substrate binding. The structure does not include residues 97-128, which corresponds to a locally unstable part of the NTR from E. coli, and might be involved in cofactor binding. Comparison of H pylori RdxA to other oxidoreductases of known structure suggests RdxA may belong to a new subgroup of oxidoreductases in which a cysteine sidechain close to the FMN cofactor could be involved in the reductive activity. In this respect, mutation of C159 to A or S (C159A/S) has resulted in loss of MTZ reductase activity, but not NADPH oxidase activity. The RdxA structure allows interpretation of the many loss-of-function mutations previously described, including those affecting C159, a residue whose interaction with FMN is required for nitroreduction of MTZ. Our studies provide unique insights into the redox behavior of the flavin in this key enzyme for metronidazole activation, and with potential use in gene therapy. (c) 2012 The Authors Journal compilation (c) 2012 FEBS.
Structure of RdxA: an oxygen insensitive nitroreductase essential for metronidazole activation in Helicobacter pylori.,Martinez-Julvez M, Rojas AL, Olekhnovich I, Angarica VE, Hoffman PS, Sancho J FEBS J. 2012 Oct 8. doi: 10.1111/febs.12020. PMID:23039228[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Goodwin A, Kersulyte D, Sisson G, Veldhuyzen van Zanten SJ, Berg DE, Hoffman PS. Metronidazole resistance in Helicobacter pylori is due to null mutations in a gene (rdxA) that encodes an oxygen-insensitive NADPH nitroreductase. Mol Microbiol. 1998 Apr;28(2):383-93. PMID:9622362
- ↑ Martinez-Julvez M, Rojas AL, Olekhnovich I, Angarica VE, Hoffman PS, Sancho J. Structure of RdxA: an oxygen insensitive nitroreductase essential for metronidazole activation in Helicobacter pylori. FEBS J. 2012 Oct 8. doi: 10.1111/febs.12020. PMID:23039228 doi:http://dx.doi.org/10.1111/febs.12020
|
