1h7x

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[[Image:1h7x.gif|left|200px]]
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{{STRUCTURE_1h7x| PDB=1h7x | SCENE= }}
{{STRUCTURE_1h7x| PDB=1h7x | SCENE= }}
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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 (DPD) FROM PIG, TERNARY COMPLEX OF A MUTANT ENZYME (C671A), NADPH AND 5-FLUOROURACIL===
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==Overview==
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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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The line below this paragraph, {{ABSTRACT_PUBMED_11179210}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 11179210 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11179210}}
==About this Structure==
==About this Structure==
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[[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 Fri May 2 18:33:02 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 06:46:33 2008''

Revision as of 03:46, 1 July 2008

Image:1h7x.png

Template:STRUCTURE 1h7x

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

Template:ABSTRACT PUBMED 11179210

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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