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| | <StructureSection load='2fvm' size='340' side='right'caption='[[2fvm]], [[Resolution|resolution]] 2.45Å' scene=''> | | <StructureSection load='2fvm' size='340' side='right'caption='[[2fvm]], [[Resolution|resolution]] 2.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2fvm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_58438 Atcc 58438]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FVM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FVM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2fvm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Lachancea_kluyveri Lachancea kluyveri]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FVM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FVM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=URP:N-(AMINOCARBONYL)-BETA-ALANINE'>URP</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]] 2.45Å</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=URP:N-(AMINOCARBONYL)-BETA-ALANINE'>URP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2fty|2fty]], [[2fvk|2fvk]], [[2ftw|2ftw]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pyd2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4934 ATCC 58438])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dihydropyrimidinase Dihydropyrimidinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.2 3.5.2.2] </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=2fvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fvm OCA], [https://pdbe.org/2fvm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fvm RCSB], [https://www.ebi.ac.uk/pdbsum/2fvm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fvm 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=2fvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fvm OCA], [https://pdbe.org/2fvm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fvm RCSB], [https://www.ebi.ac.uk/pdbsum/2fvm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fvm ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DPYS_LACK1 DPYS_LACK1]] Catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Can catalyze the ring opening of 5,6-dihydrouracil to N-carbamyl-alanine and of 5,6-dihydrothymine to N-carbamyl-amino isobutyrate.<ref>PMID:10656811</ref>
| + | [https://www.uniprot.org/uniprot/DPYS_LACK1 DPYS_LACK1] Catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Can catalyze the ring opening of 5,6-dihydrouracil to N-carbamyl-alanine and of 5,6-dihydrothymine to N-carbamyl-amino isobutyrate.<ref>PMID:10656811</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 58438]] | + | [[Category: Lachancea kluyveri]] |
| - | [[Category: Dihydropyrimidinase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dobritzsch, D]] | + | [[Category: Dobritzsch D]] |
| - | [[Category: Lohkamp, B]] | + | [[Category: Lohkamp B]] |
| - | [[Category: Beta sandwich]]
| + | |
| - | [[Category: Beta/alpha barrel]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
DPYS_LACK1 Catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Can catalyze the ring opening of 5,6-dihydrouracil to N-carbamyl-alanine and of 5,6-dihydrothymine to N-carbamyl-amino isobutyrate.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
In eukaryotes, dihydropyrimidinase catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Here we describe the three-dimensional structures of dihydropyrimidinase from two eukaryotes, the yeast Saccharomyces kluyveri and the slime mold Dictyostelium discoideum, determined and refined to 2.4 and 2.05 angstroms, respectively. Both enzymes have a (beta/alpha)8-barrel structural core embedding the catalytic di-zinc center, which is accompanied by a smaller beta-sandwich domain. Despite loop-forming insertions in the sequence of the yeast enzyme, the overall structures and architectures of the active sites of the dihydropyrimidinases are strikingly similar to each other, as well as to those of hydantoinases, dihydroorotases, and other members of the amidohydrolase superfamily of enzymes. However, formation of the physiologically relevant tetramer shows subtle but nonetheless significant differences. The extension of one of the sheets of the beta-sandwich domain across a subunit-subunit interface in yeast dihydropyrimidinase underlines its closer evolutionary relationship to hydantoinases, whereas the slime mold enzyme shows higher similarity to the noncatalytic collapsin-response mediator proteins involved in neuron development. Catalysis is expected to follow a dihydroorotase-like mechanism but in the opposite direction and with a different substrate. Complexes with dihydrouracil and N-carbamyl-beta-alanine obtained for the yeast dihydropyrimidinase reveal the mode of substrate and product binding and allow conclusions about what determines substrate specificity, stereoselectivity, and the reaction direction among cyclic amidohydrolases.
The crystal structures of dihydropyrimidinases reaffirm the close relationship between cyclic amidohydrolases and explain their substrate specificity.,Lohkamp B, Andersen B, Piskur J, Dobritzsch D J Biol Chem. 2006 May 12;281(19):13762-76. Epub 2006 Mar 3. PMID:16517602[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gojkovic Z, Jahnke K, Schnackerz KD, Piskur J. PYD2 encodes 5,6-dihydropyrimidine amidohydrolase, which participates in a novel fungal catabolic pathway. J Mol Biol. 2000 Jan 28;295(4):1073-87. PMID:10656811 doi:http://dx.doi.org/10.1006/jmbi.1999.3393
- ↑ Lohkamp B, Andersen B, Piskur J, Dobritzsch D. The crystal structures of dihydropyrimidinases reaffirm the close relationship between cyclic amidohydrolases and explain their substrate specificity. J Biol Chem. 2006 May 12;281(19):13762-76. Epub 2006 Mar 3. PMID:16517602 doi:http://dx.doi.org/10.1074/jbc.M513266200
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