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1h7x

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[[Image:1h7x.gif|left|200px]]<br />
 
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<applet load="1h7x" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1h7x, resolution 2.01&Aring;" />
 
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'''DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, TERNARY COMPLEX OF A MUTANT ENZYME (C671A), NADPH AND 5-FLUOROURACIL'''<br />
 
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==Overview==
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==Dihydropyrimidine dehydrogenase (DPD) from pig, ternary complex of a mutant enzyme (C671A), NADPH and 5-fluorouracil==
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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.
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<StructureSection load='1h7x' size='340' side='right'caption='[[1h7x]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<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>
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1H7X is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with SF4, FMN, FAD, NDP and URF as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Structure known Active Site: AC5. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1H7X OCA].
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</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>
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<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>
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==Reference==
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<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>
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=11179210 11179210]
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</table>
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[[Category: Dihydropyrimidine dehydrogenase (NADP(+))]]
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== Function ==
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[[Category: Single protein]]
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h7/1h7x_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=1h7x ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Sus scrofa]]
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[[Category: Dobritzsch, D.]]
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[[Category: Dobritzsch D]]
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[[Category: Lindqvist, Y.]]
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[[Category: Lindqvist Y]]
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[[Category: Schnackerz, K.D.]]
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[[Category: Schnackerz KD]]
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[[Category: Schneider, G.]]
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[[Category: Schneider G]]
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[[Category: FAD]]
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[[Category: FMN]]
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[[Category: NDP]]
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[[Category: SF4]]
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[[Category: URF]]
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[[Category: 5-fluorouracil degradation]]
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[[Category: electron transfer]]
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[[Category: flavin]]
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[[Category: iron-sulfur clusters]]
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[[Category: oxidoreductase]]
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[[Category: pyrimidine catabolism]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 12:33:56 2007''
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Current revision

Dihydropyrimidine dehydrogenase (DPD) from pig, ternary complex of a mutant enzyme (C671A), NADPH and 5-fluorouracil

PDB ID 1h7x

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