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| | <StructureSection load='3upy' size='340' side='right' caption='[[3upy]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='3upy' size='340' side='right' caption='[[3upy]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3upy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Brucella_melitensis_biovar_abortus_2308 Brucella melitensis biovar abortus 2308]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UPY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UPY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3upy]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UPY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UPY FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FOM:3-[FORMYL(HYDROXY)AMINO]PROPYLPHOSPHONIC+ACID'>FOM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><br> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FOM:3-[FORMYL(HYDROXY)AMINO]PROPYLPHOSPHONIC+ACID'>FOM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3upl|3upl]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3upl|3upl]]</td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BAB2_0264, DRL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=359391 Brucella melitensis biovar Abortus 2308])</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=3upy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3upy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3upy RCSB], [http://www.ebi.ac.uk/pdbsum/3upy PDBsum]</span></td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3upy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3upy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3upy RCSB], [http://www.ebi.ac.uk/pdbsum/3upy PDBsum]</span></td></tr>
| + | </table> |
| - | <table> | + | |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brucella melitensis biovar abortus 2308]]
| + | [[Category: Calisto, B M]] |
| - | [[Category: Calisto, B M.]] | + | [[Category: Fita, I]] |
| - | [[Category: Fita, I.]] | + | [[Category: Perez-Gil, J]] |
| - | [[Category: Perez-Gil, J.]] | + | |
| | [[Category: Rodriguez-Concepcion, M]] | | [[Category: Rodriguez-Concepcion, M]] |
| | [[Category: Nadph binding]] | | [[Category: Nadph binding]] |
| | [[Category: Oxidoreductase]] | | [[Category: Oxidoreductase]] |
| | [[Category: Rossmann fold]] | | [[Category: Rossmann fold]] |
| Structural highlights
Publication Abstract from PubMed
Most bacteria use the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for the synthesis of their essential isoprenoid precursors. The absence of the MEP pathway in humans makes it a promising new target for the development of much needed new and safe antimicrobial drugs. However, bacteria show a remarkable metabolic plasticity for isoprenoid production. For example, the NADPH-dependent production of MEP from 1-deoxy-D-xylulose 5-phosphate in the first committed step of the MEP pathway is catalyzed by 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in most bacteria, whereas an unrelated DXR-like (DRL) protein was recently found to catalyze the same reaction in some organisms, including the emerging human and animal pathogens Bartonella and Brucella. Here, we report the x-ray crystal structures of the Brucella abortus DRL enzyme in its apo form and in complex with the broad-spectrum antibiotic fosmidomycin solved to 1.5 and 1.8 A resolution, respectively. DRL is a dimer, with each polypeptide folding into three distinct domains starting with the NADPH-binding domain, in resemblance to the structure of bacterial DXR enzymes. Other than that, DRL and DXR show a low structural relationship, with a different disposition of the domains and a topologically unrelated C-terminal domain. In particular, the active site of DRL presents a unique arrangement, suggesting that the design of drugs that would selectively inhibit DRL-harboring pathogens without affecting beneficial or innocuous bacteria harboring DXR should be feasible. As a proof of concept, we identified two strong DXR inhibitors that have virtually no effect on DRL activity.
Crystal structure of Brucella abortus deoxyxylulose-5-phosphate reductoisomerase-like (DRL) enzyme involved in isoprenoid biosynthesis.,Perez-Gil J, Calisto BM, Behrendt C, Kurz T, Fita I, Rodriguez-Concepcion M J Biol Chem. 2012 May 4;287(19):15803-9. Epub 2012 Mar 22. PMID:22442144[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Perez-Gil J, Calisto BM, Behrendt C, Kurz T, Fita I, Rodriguez-Concepcion M. Crystal structure of Brucella abortus deoxyxylulose-5-phosphate reductoisomerase-like (DRL) enzyme involved in isoprenoid biosynthesis. J Biol Chem. 2012 May 4;287(19):15803-9. Epub 2012 Mar 22. PMID:22442144 doi:10.1074/jbc.M112.354811
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