1gth

<table><tr><td colspan='2'>[[1gth]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pig Pig]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GTH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GTH FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dihydropyrimidine_dehydrogenase_(NADP(+)) Dihydropyrimidine dehydrogenase (NADP(+))], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.2 1.3.1.2] </span></td></tr>

[[https://www.uniprot.org/uniprot/DPYD_PIG DPYD_PIG]] Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine.<ref>PMID:9860876</ref> <ref>PMID:20831907</ref> <ref>PMID:11179210</ref>

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== Publication Abstract from PubMed ==

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.

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<ref>PMID:11796730</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 1gth" style="background-color:#fffaf0;"></div>

[[Category: Pig]]

[[Category: Dobritzsch, D]]

[[Category: Lindqvist, Y]]

[[Category: Ricagno, S]]

[[Category: Schnackerz, K D]]

[[Category: Schneider, G]]

[[Category: Pyrimidine catabolism]]