1gte: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1gte. | [[Image:1gte.jpg|left|200px]]<br /><applet load="1gte" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1gte" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="1gte, resolution 1.65Å" /> | caption="1gte, resolution 1.65Å" /> | ||
'''DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, BINARY COMPLEX WITH 5-IODOURACIL'''<br /> | '''DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, BINARY COMPLEX WITH 5-IODOURACIL'''<br /> | ||
| Line 8: | Line 7: | ||
==About this Structure== | ==About this Structure== | ||
1GTE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with SF4, FMN, FAD and IUR as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] | 1GTE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with SF4, FMN, FAD and IUR as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Site: <scene name='pdbsite=FA1:Iur Binding Site For Chain D'>FA1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GTE OCA]. | ||
==Reference== | ==Reference== | ||
| Line 31: | Line 30: | ||
[[Category: pyrimidine catabolism]] | [[Category: pyrimidine catabolism]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 15:35:34 2007'' | ||
Revision as of 16:25, 18 December 2007
|
DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, BINARY COMPLEX WITH 5-IODOURACIL
OverviewOverview
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 StructureAbout this Structure
1GTE is a Single protein structure of sequence from Sus scrofa with SF4, FMN, FAD and IUR as ligands. Active as Dihydropyrimidine dehydrogenase (NADP(+)), with EC number 1.3.1.2 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
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 Tue Dec 18 15:35:34 2007