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| <StructureSection load='1c3v' size='340' side='right'caption='[[1c3v]], [[Resolution|resolution]] 2.39Å' scene=''> | | <StructureSection load='1c3v' size='340' side='right'caption='[[1c3v]], [[Resolution|resolution]] 2.39Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[1c3v]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C3V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C3V FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1c3v]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C3V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C3V FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=PDC:PYRIDINE-2,6-DICARBOXYLIC+ACID'>PDC</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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]] 2.39Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1p9l|1p9l]]</div></td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=PDC:PYRIDINE-2,6-DICARBOXYLIC+ACID'>PDC</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/4-hydroxy-tetrahydrodipicolinate_reductase 4-hydroxy-tetrahydrodipicolinate reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.1.8 1.17.1.8] </span></td></tr>
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| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1c3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c3v OCA], [https://pdbe.org/1c3v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c3v RCSB], [https://www.ebi.ac.uk/pdbsum/1c3v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c3v 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=1c3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c3v OCA], [https://pdbe.org/1c3v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c3v RCSB], [https://www.ebi.ac.uk/pdbsum/1c3v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c3v ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
| [[https://www.uniprot.org/uniprot/DAPB_MYCTU DAPB_MYCTU]] Catalyzes the conversion of 4-hydroxy-tetrahydrodipicolinate (HTPA) to tetrahydrodipicolinate (Probable). Can use both NADH and NADPH as a reductant, with NADH being 6-fold as effective as NADPH.<ref>PMID:12962488</ref>
| | [https://www.uniprot.org/uniprot/DAPB_MYCTU DAPB_MYCTU] Catalyzes the conversion of 4-hydroxy-tetrahydrodipicolinate (HTPA) to tetrahydrodipicolinate (Probable). Can use both NADH and NADPH as a reductant, with NADH being 6-fold as effective as NADPH.<ref>PMID:12962488</ref> |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| </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=1c3v ConSurf]. | | </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=1c3v ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Dihydrodipicolinate reductase (DHPR) catalyzes the reduced pyridine nucleotide-dependent reduction of the alpha,beta-unsaturated cyclic imine, dihydrodipicolinate, to generate tetrahydrodipicolinate. This enzyme catalyzes the second step in the bacterial biosynthetic pathway that generates meso-diaminopimelate, a component of bacterial cell walls, and the amino acid L-lysine. The Mycobacterium tuberculosis dapB-encoded DHPR has been cloned, expressed, purified, and crystallized in two ternary complexes with NADH or NADPH and the inhibitor 2,6-pyridinedicarboxylate (2,6-PDC). The structures have been solved using molecular replacement strategies, and the DHPR-NADH-2,6-PDC and DHPR-NADPH-2,6-PDC complexes have been refined against data to 2.3 and 2.5 A, respectively. The M. tuberculosis DHPR is a tetramer of identical subunits, with each subunit composed of two domains connected by two flexible hinge regions. The N-terminal domain binds pyridine nucleotide, while the C-terminal domain is involved in both tetramer formation and substrate/inhibitor binding. The M. tuberculosis DHPR uses NADH and NADPH with nearly equal efficiency based on V/K values. To probe the nature of this substrate specificity, we have generated two mutants, K9A and K11A, residues that are close to the 2'-phosphate of NADPH. These two mutants exhibit decreased specificity for NADPH by factors of 6- and 30-fold, respectively, but the K11A mutant exhibits 270% of WT activity using NADH. The highly conserved structure of the nucleotide fold may permit other enzyme's nucleotide specificity to be altered using similar mutagenic strategies.
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| The three-dimensional structures of the Mycobacterium tuberculosis dihydrodipicolinate reductase-NADH-2,6-PDC and -NADPH-2,6-PDC complexes. Structural and mutagenic analysis of relaxed nucleotide specificity.,Cirilli M, Zheng R, Scapin G, Blanchard JS Biochemistry. 2003 Sep 16;42(36):10644-50. PMID:12962488<ref>PMID:12962488</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 1c3v" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: 4-hydroxy-tetrahydrodipicolinate reductase]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Blanchard, J S]] | | [[Category: Mycobacterium tuberculosis]] |
| [[Category: Cirilli, M]] | | [[Category: Blanchard JS]] |
| [[Category: Scapin, G]] | | [[Category: Cirilli M]] |
| [[Category: Structural genomic]] | | [[Category: Scapin G]] |
| [[Category: Zheng, R]] | | [[Category: Zheng R]] |
| [[Category: Oxidoreductase]]
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| [[Category: PSI, Protein structure initiative]]
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| [[Category: Tbsgc]]
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| [[Category: Two-domain structure]]
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