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| [[Image:1h7x.gif|left|200px]] | | {{Seed}} |
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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'''
| | ===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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_11179210}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11179210 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11179210}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Oxidoreductase]] | | [[Category: Oxidoreductase]] |
| [[Category: Pyrimidine catabolism]] | | [[Category: Pyrimidine catabolism]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:33:02 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 06:46:33 2008'' |