View source for 1gte

[[Image:1gte.jpg|left|200px]]

 {{Structure
|PDB= 1gte |SIZE=350|CAPTION= <scene name='initialview01'>1gte</scene>, resolution 1.65&Aring;
|SITE= <scene name='pdbsite=FA1:Iur+Binding+Site+For+Chain+D'>FA1</scene>
|LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=IUR:5-IODOURACIL'>IUR</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>
|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= 
|DOMAIN=
|RELATEDENTRY=
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1gte FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gte OCA], [http://www.ebi.ac.uk/pdbsum/1gte PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1gte RCSB]</span>
}}

'''DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, BINARY COMPLEX WITH 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==
1GTE 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=1GTE 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:[http://www.ncbi.nlm.nih.gov/pubmed/11796730 11796730]
[[Category: Dihydropyrimidine dehydrogenase (NADP(+))]]
[[Category: Single protein]]
[[Category: Sus scrofa]]
[[Category: Dobritzsch, D.]]
[[Category: Lindqvist, Y.]]
[[Category: Ricagno, S.]]
[[Category: Schnackerz, K D.]]
[[Category: Schneider, G.]]
[[Category: 5-fluorouracil degradation]]
[[Category: electron transfer]]
[[Category: flavin]]
[[Category: iron-sulfur cluster]]
[[Category: oxidoreductase]]
[[Category: pyrimidine catabolism]]

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