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| | <StructureSection load='6klk' size='340' side='right'caption='[[6klk]], [[Resolution|resolution]] 1.76Å' scene=''> | | <StructureSection load='6klk' size='340' side='right'caption='[[6klk]], [[Resolution|resolution]] 1.76Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6klk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KLK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KLK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6klk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KLK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KLK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=URF:5-FLUOROURACIL'>URF</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]] 1.759Å</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=URF:5-FLUOROURACIL'>URF</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydropyrimidinase Dihydropyrimidinase], with EC number [http://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=6klk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6klk OCA], [https://pdbe.org/6klk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6klk RCSB], [https://www.ebi.ac.uk/pdbsum/6klk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6klk ProSAT]</span></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=6klk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6klk OCA], [http://pdbe.org/6klk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6klk RCSB], [http://www.ebi.ac.uk/pdbsum/6klk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6klk ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HYDA_PSEAE HYDA_PSEAE]] Catalyzes the hydrolysis of dihydropyrimidines and of the structurally related DL-5-mono-substituted hydantoins, to produce N-carbamoyl-D-amino acids. | + | [https://www.uniprot.org/uniprot/HYDA_PSEAE HYDA_PSEAE] Catalyzes the hydrolysis of dihydropyrimidines and of the structurally related DL-5-mono-substituted hydantoins, to produce N-carbamoyl-D-amino acids. |
| | <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: Dihydropyrimidinase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chen, I C]] | + | [[Category: Pseudomonas aeruginosa PAO1]] |
| - | [[Category: Huang, C Y]] | + | [[Category: Chen IC]] |
| - | [[Category: Huang, Y H]] | + | [[Category: Huang CY]] |
| - | [[Category: Hydrolase]] | + | [[Category: Huang YH]] |
| Structural highlights
Function
HYDA_PSEAE Catalyzes the hydrolysis of dihydropyrimidines and of the structurally related DL-5-mono-substituted hydantoins, to produce N-carbamoyl-D-amino acids.
Publication Abstract from PubMed
Dihydropyrimidinase (DHPase) catalyzes the reversible cyclization of dihydrouracil to N-carbamoyl-beta-alanine in the second step of the pyrimidine degradation pathway. Whether 5-fluorouracil (5-FU), the best-known fluoropyrimidine that is used to target the enzyme thymidylate synthase for anticancer therapy, can bind to DHPase remains unknown. In this study, we found that 5-FU can form a stable complex with Pseudomonas aeruginosa DHPase (PaDHPase). The crystal structure of PaDHPase complexed with 5-FU was determined at 1.76A resolution (PDB entry 6KLK). Various interactions between 5-FU and PaDHPase were examined. Six residues, namely, His61, Tyr155, Asp316, Cys318, Ser289 and Asn337, of PaDHPase were involved in 5-FU binding. Except for Cys318, these residues are also known as the substrate-binding sites of DHPase. 5-FU interacts with the main chains of residues Ser289 (3.0A) and Asn337 (3.2A) and the side chains of residues Tyr155 (2.8A) and Cys318 (2.9A). Mutation at either Tyr155 or Cys318 of PaDHPase caused a low 5-FU binding activity of PaDHPase. This structure and the binding mode provided molecular insights into how the dimetal center in DHPase undergoes a conformational change during 5-FU binding. Further research can directly focus on revisiting the role of DHPase in anticancer therapy.
Crystal structure of dihydropyrimidinase in complex with anticancer drug 5-fluorouracil.,Huang YH, Ning ZJ, Huang CY Biochem Biophys Res Commun. 2019 Oct 29;519(1):160-165. doi:, 10.1016/j.bbrc.2019.08.153. Epub 2019 Aug 31. PMID:31481233[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Huang YH, Ning ZJ, Huang CY. Crystal structure of dihydropyrimidinase in complex with anticancer drug 5-fluorouracil. Biochem Biophys Res Commun. 2019 Oct 29;519(1):160-165. doi:, 10.1016/j.bbrc.2019.08.153. Epub 2019 Aug 31. PMID:31481233 doi:http://dx.doi.org/10.1016/j.bbrc.2019.08.153
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