This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1gte
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1gte.jpg|left|200px]] | [[Image:1gte.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1gte", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_1gte| PDB=1gte | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, BINARY COMPLEX WITH 5-IODOURACIL''' | '''DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, BINARY COMPLEX WITH 5-IODOURACIL''' | ||
| Line 23: | Line 20: | ||
==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://www.ncbi.nlm.nih.gov/pubmed/11796730 11796730] | 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: Single protein]] | ||
[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
| Line 32: | Line 28: | ||
[[Category: Schneider, G.]] | [[Category: Schneider, G.]] | ||
[[Category: 5-fluorouracil degradation]] | [[Category: 5-fluorouracil degradation]] | ||
| - | [[Category: | + | [[Category: Electron transfer]] |
| - | [[Category: | + | [[Category: Flavin]] |
| - | [[Category: | + | [[Category: Iron-sulfur cluster]] |
| - | [[Category: | + | [[Category: Oxidoreductase]] |
| - | [[Category: | + | [[Category: Pyrimidine catabolism]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:59:05 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 14:59, 2 May 2008
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 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 Fri May 2 17:59:05 2008
