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| | <StructureSection load='2x1j' size='340' side='right'caption='[[2x1j]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='2x1j' size='340' side='right'caption='[[2x1j]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2x1j]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_radiodurans"_raj_et_al._1960 "micrococcus radiodurans" raj et al. 1960]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X1J OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2X1J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2x1j]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"micrococcus_radiodurans"_raj_et_al._1960 "micrococcus radiodurans" raj et al. 1960]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X1J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X1J FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr> | | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1w3q|1w3q]], [[2vpa|2vpa]], [[1w3o|1w3o]], [[1w3p|1w3p]], [[1w3r|1w3r]], [[2x1k|2x1k]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1w3q|1w3q]], [[2vpa|2vpa]], [[1w3o|1w3o]], [[1w3p|1w3p]], [[1w3r|1w3r]], [[2x1k|2x1k]]</div></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2x1j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x1j OCA], [http://pdbe.org/2x1j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2x1j RCSB], [http://www.ebi.ac.uk/pdbsum/2x1j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2x1j 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=2x1j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x1j OCA], [https://pdbe.org/2x1j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x1j RCSB], [https://www.ebi.ac.uk/pdbsum/2x1j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x1j ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| Structural highlights
Publication Abstract from PubMed
Metronidazole (MTZ) is an antibiotic commonly used to treat anaerobic bacterial infections in humans and animals. Antibiotic resistance toward this class of 5-nitroimidazole (5-Ni) drug derivatives has been related to the Nim genes thought to encode a reductase. Here we report the biophysical characteristics of the NimA protein from Deinococcus radiodurans (DrNimA) binding to MTZ and three other 5-Ni drugs. The interaction energies of the protein and antibiotic are studied by isothermal titration calorimetry (ITC) and with free energy and linear interaction energy (LIE) calculations, where the latter method revealed that the antibiotic binding is mainly of hydrophobic character. ITC measurements further found that one DrNimA dimer has two antibiotic binding sites which were not affected by mutation of the reactive His71. The observed association constants (K(a)) were in the range of 5.1-4910(4)M(-1) and the enthalpy release upon binding to DrNimA for the four drugs studied was relatively low (approximately -1 kJ/mol) but still measurable. The drug binding is mainly entropy driven and along with the hydrophobic drug binding site found by crystallography, this possibly explains the low observed enthalpy values. The effect of the His71 mutation and the presence of MTZ were studied by differential scanning calorimetry (DSC). Native DrNimA is a yellow colored protein where the interaction from His71 to the cofactor is thought to be responsible for the coloring. Mutations of His71 to Ala, Ser, Leu or Asp all gave transparent, colorless protein solutions, and the two mutant crystal structures of DrNimA-H71A and DrNimA-H71S presented revealed no cofactor binding.
Biophysical characterization and mutational analysis of the antibiotic resistance protein NimA from Deinococcus radiodurans.,Leiros HK, Brandsdal BO, McSweeney SM Biochim Biophys Acta. 2010 Apr;1804(4):967-76. Epub 2010 Jan 21. PMID:20096385[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Leiros HK, Brandsdal BO, McSweeney SM. Biophysical characterization and mutational analysis of the antibiotic resistance protein NimA from Deinococcus radiodurans. Biochim Biophys Acta. 2010 Apr;1804(4):967-76. Epub 2010 Jan 21. PMID:20096385 doi:10.1016/j.bbapap.2010.01.010
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