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| - | [[Image:1c3v.gif|left|200px]] | |
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| - | {{Structure
| + | ==DIHYDRODIPICOLINATE REDUCTASE FROM MYCOBACTERIUM TUBERCULOSIS COMPLEXED WITH NADPH AND PDC== |
| - | |PDB= 1c3v |SIZE=350|CAPTION= <scene name='initialview01'>1c3v</scene>, resolution 2.39Å
| + | <StructureSection load='1c3v' size='340' side='right'caption='[[1c3v]], [[Resolution|resolution]] 2.39Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <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> | + | <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> |
| - | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrodipicolinate_reductase Dihydrodipicolinate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.26 1.3.1.26] </span>
| + | </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> |
| - | |GENE=
| + | <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> |
| - | |DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam05173 DapB_C], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam01113 DapB_N]</span>
| + | <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> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c3v OCA], [http://www.ebi.ac.uk/pdbsum/1c3v PDBsum], [http://www.fli-leibniz.de/cgi-bin/ImgLib.pl?CODE=1kfv JenaLib], [http://www.rcsb.org/pdb/explore.do?structureId=1c3v RCSB]</span>
| + | </table> |
| - | }}
| + | == 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> |
| - | '''DIHYDRODIPICOLINATE REDUCTASE FROM MYCOBACTERIUM TUBERCULOSIS COMPLEXED WITH NADPH AND PDC'''
| + | == Evolutionary Conservation == |
| - | | + | [[Image:Consurf_key_small.gif|200px|right]] |
| - | | + | Check<jmol> |
| - | ==Overview== | + | <jmolCheckbox> |
| - | 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.
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c3/1c3v_consurf.spt"</scriptWhenChecked> |
| - | | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | ==About this Structure== | + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | 1C3V is a [[Single protein]] structure of sequence from [http://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].
| + | </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=1c3v ConSurf]. |
| - | ==Reference== | + | <div style="clear:both"></div> |
| - | 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:[http://www.ncbi.nlm.nih.gov/pubmed/12962488 12962488]
| + | == References == |
| - | [[Category: Dihydrodipicolinate reductase]] | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mycobacterium tuberculosis]] | | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Single protein]]
| + | [[Category: Blanchard JS]] |
| - | [[Category: Blanchard, J S.]] | + | [[Category: Cirilli M]] |
| - | [[Category: Cirilli, M.]] | + | [[Category: Scapin G]] |
| - | [[Category: Scapin, G.]] | + | [[Category: Zheng R]] |
| - | [[Category: TBSGC, TB Structural Genomics Consortium.]]
| + | |
| - | [[Category: Zheng, R.]] | + | |
| - | [[Category: protein structure initiative]]
| + | |
| - | [[Category: psi]]
| + | |
| - | [[Category: structural genomic]]
| + | |
| - | [[Category: tb structural genomics consortium]]
| + | |
| - | [[Category: tbsgc]]
| + | |
| - | [[Category: two-domain structure]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 26 05:51:08 2008''
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