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| <StructureSection load='1j79' size='340' side='right'caption='[[1j79]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='1j79' size='340' side='right'caption='[[1j79]], [[Resolution|resolution]] 1.70Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[1j79]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J79 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1J79 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1j79]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1J79 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1J79 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NCD:N-CARBAMOYL-L-ASPARTATE'>NCD</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.7Å</td></tr> |
| <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=NCD:N-CARBAMOYL-L-ASPARTATE'>NCD</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PYRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=1j79 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j79 OCA], [https://pdbe.org/1j79 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1j79 RCSB], [https://www.ebi.ac.uk/pdbsum/1j79 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1j79 ProSAT]</span></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydroorotase Dihydroorotase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.3 3.5.2.3] </span></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=1j79 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j79 OCA], [http://pdbe.org/1j79 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1j79 RCSB], [http://www.ebi.ac.uk/pdbsum/1j79 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1j79 ProSAT]</span></td></tr> | |
| </table> | | </table> |
| | == Function == |
| | [https://www.uniprot.org/uniprot/PYRC_ECOLI PYRC_ECOLI] |
| == 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=1j79 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=1j79 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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| Dihydroorotase plays a key role in pyrimidine biosynthesis by catalyzing the reversible interconversion of carbamoyl aspartate to dihydroorotate. Here we describe the three-dimensional structure of dihydroorotase from Escherichia coli determined and refined to 1.7 A resolution. Each subunit of the homodimeric enzyme folds into a "TIM" barrel motif with eight strands of parallel beta-sheet flanked on the outer surface by alpha-helices. Unexpectedly, each subunit contains a binuclear zinc center with the metal ions separated by approximately 3.6 A. Lys 102, which is carboxylated, serves as a bridging ligand between the two cations. The more buried or alpha-metal ion in subunit I is surrounded by His 16, His 18, Lys 102, Asp 250, and a solvent molecule (most likely a hydroxide ion) in a trigonal bipyramidal arrangement. The beta-metal ion, which is closer to the solvent, is tetrahedrally ligated by Lys 102, His 139, His 177, and the bridging hydroxide. L-Dihydroorotate is observed bound to subunit I, with its carbonyl oxygen, O4, lying 2.9 A from the beta-metal ion. Important interactions for positioning dihydroorotate into the active site include a salt bridge with the guanidinium group of Arg 20 and various additional electrostatic interactions with both protein backbone and side chain atoms. Strikingly, in subunit II, carbamoyl L-aspartate is observed binding near the binuclear metal center with its carboxylate side chain ligating the two metals and thus displacing the bridging hydroxide ion. From the three-dimensional structures of the enzyme-bound substrate and product, it has been possible to propose a unique catalytic mechanism for dihydroorotase. In the direction of dihydroorotate hydrolysis, the bridging hydroxide attacks the re-face of dihydroorotate with general base assistance by Asp 250. The carbonyl group is polarized for nucleophilic attack by the bridging hydroxide through a direct interaction with the beta-metal ion. During the cyclization of carbamoyl aspartate, Asp 250 initiates the reaction by abstracting a proton from N3 of the substrate. The side chain carboxylate of carbamoyl aspartate is polarized through a direct electrostatic interaction with the binuclear metal center. The ensuing tetrahedral intermediate collapses with C-O bond cleavage and expulsion of the hydroxide which then bridges the binuclear metal center.
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| Molecular structure of dihydroorotase: a paradigm for catalysis through the use of a binuclear metal center.,Thoden JB, Phillips GN Jr, Neal TM, Raushel FM, Holden HM Biochemistry. 2001 Jun 19;40(24):6989-97. PMID:11401542<ref>PMID:11401542</ref>
| | ==See Also== |
| | | *[[Dihydroorotase 3D structures|Dihydroorotase 3D structures]] |
| 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 1j79" style="background-color:#fffaf0;"></div>
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| == References == | |
| <references/>
| |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Bacillus coli migula 1895]] | | [[Category: Escherichia coli]] |
| [[Category: Dihydroorotase]]
| |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Holden, H M]] | | [[Category: Holden HM]] |
| [[Category: Neal, T M]] | | [[Category: Neal TM]] |
| [[Category: Phillips, G N]] | | [[Category: Phillips Jr GN]] |
| [[Category: Raushel, F M]] | | [[Category: Raushel FM]] |
| [[Category: Thoden, J B]] | | [[Category: Thoden JB]] |
| [[Category: Hydrolase]]
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| [[Category: Metalloenzyme]]
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| [[Category: Pyrimidine biosynthesis]]
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| [[Category: Tim barrel]]
| |