1h7x

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[[Image:1h7x.gif|left|200px]]<br /><applet load="1h7x" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1h7x.gif|left|200px]]
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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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{{Structure
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|PDB= 1h7x |SIZE=350|CAPTION= <scene name='initialview01'>1h7x</scene>, resolution 2.01&Aring;
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|SITE= <scene name='pdbsite=AC5:Urf+Binding+Site+For+Chain+D'>AC5</scene>
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|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>
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|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]
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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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'''DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, TERNARY COMPLEX OF A MUTANT ENZYME (C671A), NADPH AND 5-FLUOROURACIL'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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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 <scene name='pdbligand=SF4:'>SF4</scene>, <scene name='pdbligand=FMN:'>FMN</scene>, <scene name='pdbligand=FAD:'>FAD</scene>, <scene name='pdbligand=NDP:'>NDP</scene> and <scene name='pdbligand=URF:'>URF</scene> 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] Known structural/functional Site: <scene name='pdbsite=AC5:Urf+Binding+Site+For+Chain+D'>AC5</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H7X OCA].
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1H7X 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].
==Reference==
==Reference==
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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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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]
[[Category: Dihydropyrimidine dehydrogenase (NADP(+))]]
[[Category: Dihydropyrimidine dehydrogenase (NADP(+))]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: electron transfer]]
[[Category: electron transfer]]
[[Category: flavin]]
[[Category: flavin]]
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[[Category: iron-sulfur clusters]]
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[[Category: iron-sulfur cluster]]
[[Category: oxidoreductase]]
[[Category: oxidoreductase]]
[[Category: pyrimidine catabolism]]
[[Category: pyrimidine catabolism]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:58:24 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:33:29 2008''

Revision as of 09:33, 20 March 2008

Image:1h7x.gif


PDB ID 1h7x

Drag the structure with the mouse to rotate
, resolution 2.01Å
Sites:
Ligands: , , , and
Gene: DPYD (Sus scrofa)
Activity: Dihydropyrimidine dehydrogenase (NADP(+)), with EC number 1.3.1.2
Coordinates: save as pdb, mmCIF, xml



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

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