1h7x: Difference between revisions

← Older edit Newer edit →

Revision as of 12:33, 20 March 2008

File:1h7x.gif

, resolution 2.01Å

Sites:

Ligands:

, , , and

Gene:

DPYD (Sus scrofa)

Activity:

Dihydropyrimidine dehydrogenase (NADP(+)), with EC number 1.3.1.2

Coordinates:

save as pdb, mmCIF, xml

DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, TERNARY COMPLEX OF A MUTANT ENZYME (C671A), NADPH AND 5-FLUOROURACIL

OverviewOverview

Dihydropyrimidine dehydrogenase catalyzes the first step in pyrimidine degradation: the NADPH-dependent reduction of uracil and thymine to the corresponding 5,6-dihydropyrimidines. Its controlled inhibition has become an adjunct target for cancer therapy, since the enzyme is also responsible for the rapid breakdown of the chemotherapeutic drug 5-fluorouracil. The crystal structure of the homodimeric pig liver enzyme (2x 111 kDa) determined at 1.9 A resolution reveals a highly modular subunit organization, consisting of five domains with different folds. Dihydropyrimidine dehydrogenase contains two FAD, two FMN and eight [4Fe-4S] clusters, arranged in two electron transfer chains that pass the dimer interface twice. Two of the Fe-S clusters show a hitherto unobserved coordination involving a glutamine residue. The ternary complex of an inactive mutant of the enzyme with bound NADPH and 5-fluorouracil reveals the architecture of the substrate-binding sites and residues responsible for recognition and binding of the drug.

About this StructureAbout this Structure

1H7X is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fluorouracil., Dobritzsch D, Schneider G, Schnackerz KD, Lindqvist Y, EMBO J. 2001 Feb 15;20(4):650-60. PMID:11179210

Page seeded by OCA on Thu Mar 20 11:33:29 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1h7x.gif|left|200px]]<br /><applet load="1h7x" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:1h7x.gif|left|200px]]
-caption="1h7x, resolution 2.01&Aring;" />
-'''DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, TERNARY COMPLEX OF A MUTANT ENZYME (C671A), NADPH AND 5-FLUOROURACIL'''<br />
+ {{Structure
+|PDB= 1h7x |SIZE=350|CAPTION= <scene name='initialview01'>1h7x</scene>, resolution 2.01&Aring;
+|SITE= <scene name='pdbsite=AC5:Urf+Binding+Site+For+Chain+D'>AC5</scene>
+|LIGAND= <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene> and <scene name='pdbligand=URF:5-FLUOROURACIL'>URF</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]
+|GENE= DPYD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 Sus scrofa])
+}}
+'''DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG, TERNARY COMPLEX OF A MUTANT ENZYME (C671A), NADPH AND 5-FLUOROURACIL'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-H7X 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 <scene name='pdbligand=SF4:'>SF4</scene>, <scene name='pdbligand=FMN:'>FMN</scene>, <scene name='pdbligand=FAD:'>FAD</scene>, <scene name='pdbligand=NDP:'>NDP</scene> and <scene name='pdbligand=URF:'>URF</scene> 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=AC5:Urf+Binding+Site+For+Chain+D'>AC5</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H7X OCA].
+H7X 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=1H7X OCA].
 ==Reference==
-Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fluorouracil., Dobritzsch D, Schneider G, Schnackerz KD, Lindqvist Y, EMBO J. 2001 Feb 15;20(4):650-60. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11179210 11179210]
+Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fluorouracil., Dobritzsch D, Schneider G, Schnackerz KD, Lindqvist Y, EMBO J. 2001 Feb 15;20(4):650-60. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11179210 11179210]
 [[Category: Dihydropyrimidine dehydrogenase (NADP(+))]]
 [[Category: Single protein]]
@@ Line 26: / Line 35: @@
 [[Category: electron transfer]]
 [[Category: flavin]]
-[[Category: iron-sulfur clusters]]
+[[Category: iron-sulfur cluster]]
 [[Category: oxidoreductase]]
 [[Category: pyrimidine catabolism]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:58:24 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:33:29 2008''