1gth
From Proteopedia
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| - | [[Image:1gth.gif|left|200px]] | + | [[Image:1gth.gif|left|200px]] |
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| - | '''DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, TERNARY COMPLEX WITH NADPH AND 5-IODOURACIL''' | + | {{Structure |
| + | |PDB= 1gth |SIZE=350|CAPTION= <scene name='initialview01'>1gth</scene>, resolution 2.25Å | ||
| + | |SITE= <scene name='pdbsite=FA1:Ura+Binding+Site+For+Chain+D'>FA1</scene> | ||
| + | |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>, <scene name='pdbligand=IDH:(5S)-5-IODODIHYDRO-2,4(1H,3H)-PYRIMIDINEDIONE'>IDH</scene>, <scene name='pdbligand=IUR:5-IODOURACIL'>IUR</scene> and <scene name='pdbligand=URA:URACIL'>URA</scene> | ||
| + | |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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, TERNARY COMPLEX WITH NADPH AND 5-IODOURACIL''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1GTH is a [ | + | 1GTH 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=1GTH OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structure of the productive ternary complex of dihydropyrimidine dehydrogenase with NADPH and 5-iodouracil. Implications for mechanism of inhibition and electron transfer., Dobritzsch D, Ricagno S, Schneider G, Schnackerz KD, Lindqvist Y, J Biol Chem. 2002 Apr 12;277(15):13155-66. Epub 2002 Jan 16. PMID:[http:// | + | Crystal structure of the productive ternary complex of dihydropyrimidine dehydrogenase with NADPH and 5-iodouracil. Implications for mechanism of inhibition and electron transfer., Dobritzsch D, Ricagno S, Schneider G, Schnackerz KD, Lindqvist Y, J Biol Chem. 2002 Apr 12;277(15):13155-66. Epub 2002 Jan 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11796730 11796730] |
[[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]] | ||
| - | [[Category: iron-sulfur | + | [[Category: iron-sulfur cluster]] |
[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
[[Category: pyrimidine catabolism]] | [[Category: pyrimidine catabolism]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:27:40 2008'' |
Revision as of 09:27, 20 March 2008
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| , resolution 2.25Å | |||||||
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| Sites: | |||||||
| Ligands: | , , , , , and | ||||||
| Activity: | Dihydropyrimidine dehydrogenase (NADP(+)), with EC number 1.3.1.2 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, TERNARY COMPLEX WITH NADPH AND 5-IODOURACIL
Overview
Dihydroprymidine dehydrogenase catalyzes the first and rate-limiting step in pyrimidine degradation by converting pyrimidines to the corresponding 5,6- dihydro compounds. The three-dimensional structures of a binary complex with the inhibitor 5-iodouracil and two ternary complexes with NADPH and the inhibitors 5-iodouracil and uracil-4-acetic acid were determined by x-ray crystallography. In the ternary complexes, NADPH is bound in a catalytically competent fashion, with the nicotinamide ring in a position suitable for hydride transfer to FAD. The structures provide a complete picture of the electron transfer chain from NADPH to the substrate, 5-iodouracil, spanning a distance of 56 A and involving FAD, four [Fe-S] clusters, and FMN as cofactors. The crystallographic analysis further reveals that pyrimidine binding triggers a conformational change of a flexible active-site loop in the alpha/beta-barrel domain, resulting in placement of a catalytically crucial cysteine close to the bound substrate. Loop closure requires physiological pH, which is also necessary for correct binding of NADPH. Binding of the voluminous competitive inhibitor uracil-4-acetic acid prevents loop closure due to steric hindrance. The three-dimensional structure of the ternary complex enzyme-NADPH-5-iodouracil supports the proposal that this compound acts as a mechanism-based inhibitor, covalently modifying the active-site residue Cys-671, resulting in S-(hexahydro-2,4-dioxo-5-pyrimidinyl)cysteine.
About this Structure
1GTH is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.
Reference
Crystal structure of the productive ternary complex of dihydropyrimidine dehydrogenase with NADPH and 5-iodouracil. Implications for mechanism of inhibition and electron transfer., Dobritzsch D, Ricagno S, Schneider G, Schnackerz KD, Lindqvist Y, J Biol Chem. 2002 Apr 12;277(15):13155-66. Epub 2002 Jan 16. PMID:11796730
Page seeded by OCA on Thu Mar 20 11:27:40 2008
Categories: Dihydropyrimidine dehydrogenase (NADP(+)) | Single protein | Sus scrofa | Dobritzsch, D. | Lindqvist, Y. | Ricagno, S. | Schnackerz, K D. | Schneider, G. | FAD | FMN | IDH | IUR | NDP | SF4 | URA | 5-fluorouracil degradation | Electron transfer | Flavin | Iron-sulfur cluster | Oxidoreductase | Pyrimidine catabolism
