1h7x
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Dihydropyrimidine dehydrogenase catalyzes the first step in pyrimidine | + | 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== | ==About this Structure== | ||
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[[Category: Dobritzsch, D.]] | [[Category: Dobritzsch, D.]] | ||
[[Category: Lindqvist, Y.]] | [[Category: Lindqvist, Y.]] | ||
| - | [[Category: Schnackerz, K | + | [[Category: Schnackerz, K D.]] |
[[Category: Schneider, G.]] | [[Category: Schneider, G.]] | ||
[[Category: FAD]] | [[Category: FAD]] | ||
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[[Category: pyrimidine catabolism]] | [[Category: pyrimidine catabolism]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:58:24 2008'' |
Revision as of 10:58, 21 February 2008
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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 with , , , and as ligands. Active as Dihydropyrimidine dehydrogenase (NADP(+)), with EC number 1.3.1.2 Known structural/functional Site: . 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 Thu Feb 21 12:58:24 2008
Categories: Dihydropyrimidine dehydrogenase (NADP(+)) | Single protein | Sus scrofa | Dobritzsch, D. | Lindqvist, Y. | Schnackerz, K D. | Schneider, G. | FAD | FMN | NDP | SF4 | URF | 5-fluorouracil degradation | Electron transfer | Flavin | Iron-sulfur clusters | Oxidoreductase | Pyrimidine catabolism
