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1h7x

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[[Image:1h7x.gif|left|200px]]
[[Image:1h7x.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1h7x |SIZE=350|CAPTION= <scene name='initialview01'>1h7x</scene>, resolution 2.01&Aring;
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The line below this paragraph, containing "STRUCTURE_1h7x", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=AC5:Urf+Binding+Site+For+Chain+D'>AC5</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <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>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE= DPYD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 Sus scrofa])
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-->
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|DOMAIN=
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{{STRUCTURE_1h7x| PDB=1h7x | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1h7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h7x OCA], [http://www.ebi.ac.uk/pdbsum/1h7x PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1h7x RCSB]</span>
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}}
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'''DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, TERNARY COMPLEX OF A MUTANT ENZYME (C671A), NADPH AND 5-FLUOROURACIL'''
'''DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, TERNARY COMPLEX OF A MUTANT ENZYME (C671A), NADPH AND 5-FLUOROURACIL'''
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==Reference==
==Reference==
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]
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]
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[[Category: Dihydropyrimidine dehydrogenase (NADP(+))]]
 
[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Sus scrofa]]
[[Category: Sus scrofa]]
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[[Category: Schneider, G.]]
[[Category: Schneider, G.]]
[[Category: 5-fluorouracil degradation]]
[[Category: 5-fluorouracil degradation]]
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[[Category: electron transfer]]
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[[Category: Electron transfer]]
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[[Category: flavin]]
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[[Category: Flavin]]
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[[Category: iron-sulfur cluster]]
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[[Category: Iron-sulfur cluster]]
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[[Category: oxidoreductase]]
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[[Category: Oxidoreductase]]
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[[Category: pyrimidine catabolism]]
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[[Category: Pyrimidine catabolism]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:33:02 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:59:48 2008''
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Revision as of 15:33, 2 May 2008

Template:STRUCTURE 1h7x

DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, TERNARY COMPLEX OF A MUTANT ENZYME (C671A), NADPH AND 5-FLUOROURACIL


Overview

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.

About this Structure

1H7X is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.

Reference

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:11179210 Page seeded by OCA on Fri May 2 18:33:02 2008

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