1h7x: Difference between revisions

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-[[Image:1h7x.gif|left|200px]]
- {{Structure
+==Dihydropyrimidine dehydrogenase (DPD) from pig, ternary complex of a mutant enzyme (C671A), NADPH and 5-fluorouracil==
-|PDB= 1h7x |SIZE=350|CAPTION= <scene name='initialview01'>1h7x</scene>, resolution 2.01&Aring;
+<StructureSection load='1h7x' size='340' side='right'caption='[[1h7x]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
-|SITE= <scene name='pdbsite=AC5:Urf+Binding+Site+For+Chain+D'>AC5</scene>
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene> and <scene name='pdbligand=URF:5-FLUOROURACIL'>URF</scene>
+<table><tr><td colspan='2'>[[1h7x]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H7X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H7X FirstGlance]. <br>
-|ACTIVITY= [http://en.wikipedia.org/wiki/Dihydropyrimidine_dehydrogenase_(NADP(+)) Dihydropyrimidine dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.2 1.3.1.2]
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.01&#8491;</td></tr>
-|GENE= DPYD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 Sus scrofa])
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=URF:5-FLUOROURACIL'>URF</scene></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=1h7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h7x OCA], [https://pdbe.org/1h7x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h7x RCSB], [https://www.ebi.ac.uk/pdbsum/1h7x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h7x ProSAT]</span></td></tr>
+</table>
-'''DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, TERNARY COMPLEX OF A MUTANT ENZYME (C671A), NADPH AND 5-FLUOROURACIL'''
+== Function ==
+[https://www.uniprot.org/uniprot/DPYD_PIG DPYD_PIG] Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine.<ref>PMID:9860876</ref> <ref>PMID:20831907</ref> <ref>PMID:11179210</ref>
+== Evolutionary Conservation ==
-==Overview==
+[[Image:Consurf_key_small.gif|200px|right]]
-Dihydropyrimidine dehydrogenase catalyzes the first step in pyrimidine degradation: the NADPH-dependent reduction of uracil and thymine to the corresponding 5,6-dihydropyrimidines. Its controlled inhibition has become an adjunct target for cancer therapy, since the enzyme is also responsible for the rapid breakdown of the chemotherapeutic drug 5-fluorouracil. The crystal structure of the homodimeric pig liver enzyme (2x 111 kDa) determined at 1.9 A resolution reveals a highly modular subunit organization, consisting of five domains with different folds. Dihydropyrimidine dehydrogenase contains two FAD, two FMN and eight [4Fe-4S] clusters, arranged in two electron transfer chains that pass the dimer interface twice. Two of the Fe-S clusters show a hitherto unobserved coordination involving a glutamine residue. The ternary complex of an inactive mutant of the enzyme with bound NADPH and 5-fluorouracil reveals the architecture of the substrate-binding sites and residues responsible for recognition and binding of the drug.
+Check<jmol>
+  <jmolCheckbox>
-==About this Structure==
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h7/1h7x_consurf.spt"</scriptWhenChecked>
-H7X is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H7X OCA].
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
-==Reference==
+  </jmolCheckbox>
-Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fluorouracil., Dobritzsch D, Schneider G, Schnackerz KD, Lindqvist Y, EMBO J. 2001 Feb 15;20(4):650-60. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11179210 11179210]
+</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=1h7x ConSurf].
-[[Category: Dihydropyrimidine dehydrogenase (NADP(+))]]
+<div style="clear:both"></div>
-[[Category: Single protein]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Sus scrofa]]
-[[Category: Dobritzsch, D.]]
+[[Category: Dobritzsch D]]
-[[Category: Lindqvist, Y.]]
+[[Category: Lindqvist Y]]
-[[Category: Schnackerz, K D.]]
+[[Category: Schnackerz KD]]
-[[Category: Schneider, G.]]
+[[Category: Schneider G]]
-[[Category: FAD]]
-[[Category: FMN]]
-[[Category: NDP]]
-[[Category: SF4]]
-[[Category: URF]]
-[[Category: 5-fluorouracil degradation]]
-[[Category: electron transfer]]
-[[Category: flavin]]
-[[Category: iron-sulfur cluster]]
-[[Category: oxidoreductase]]
-[[Category: pyrimidine catabolism]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:33:29 2008''