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1h7x

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Revision as of 08:24, 30 October 2007 by OCA (Talk | contribs)
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1h7x, resolution 2.01Å

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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, ... [(full description)]

About this Structure

1H7X is a [Single protein] structure of sequence from [Sus scrofa] with SF4, FMN, FAD, NDP and URF as [ligands]. Active as [Dihydropyrimidine dehydrogenase (NADP(+))], with EC number [1.3.1.2]. Structure known Active Site: AC5. 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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