1gth
From Proteopedia
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|PDB= 1gth |SIZE=350|CAPTION= <scene name='initialview01'>1gth</scene>, resolution 2.25Å | |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> | |SITE= <scene name='pdbsite=FA1:Ura+Binding+Site+For+Chain+D'>FA1</scene> | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=IDH:(5S)-5-IODODIHYDRO-2,4(1H,3H)-PYRIMIDINEDIONE'>IDH</scene>, <scene name='pdbligand=IUR:5-IODOURACIL'>IUR</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1gth FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gth OCA], [http://www.ebi.ac.uk/pdbsum/1gth PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1gth RCSB]</span> | ||
}} | }} | ||
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[[Category: Schnackerz, K D.]] | [[Category: Schnackerz, K D.]] | ||
[[Category: Schneider, G.]] | [[Category: Schneider, G.]] | ||
| - | [[Category: FAD]] | ||
| - | [[Category: FMN]] | ||
| - | [[Category: IDH]] | ||
| - | [[Category: IUR]] | ||
| - | [[Category: NDP]] | ||
| - | [[Category: SF4]] | ||
| - | [[Category: URA]] | ||
[[Category: 5-fluorouracil degradation]] | [[Category: 5-fluorouracil degradation]] | ||
[[Category: electron transfer]] | [[Category: electron transfer]] | ||
| Line 42: | Line 38: | ||
[[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 Sun Mar 30 20:50:59 2008'' |
Revision as of 17:50, 30 March 2008
| |||||||
| , resolution 2.25Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , , , , , | ||||||
| Activity: | Dihydropyrimidine dehydrogenase (NADP(+)), with EC number 1.3.1.2 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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
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