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.


1h7w

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:54, 9 May 2024) (edit) (undo)
 
(13 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1h7w.jpg|left|200px]]
 
-
{{Structure
+
==Dihydropyrimidine dehydrogenase (DPD) from pig==
-
|PDB= 1h7w |SIZE=350|CAPTION= <scene name='initialview01'>1h7w</scene>, resolution 1.90&Aring;
+
<StructureSection load='1h7w' size='340' side='right'caption='[[1h7w]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
-
|SITE= <scene name='pdbsite=AC5:Fmn+Binding+Site+For+Chain+A'>AC5</scene>, <scene name='pdbsite=AC6:Fad+Binding+Site+For+Chain+A'>AC6</scene>, <scene name='pdbsite=BC5:Fmn+Binding+Site+For+Chain+B'>BC5</scene>, <scene name='pdbsite=BC6:Fad+Binding+Site+For+Chain+B'>BC6</scene>, <scene name='pdbsite=CC5:Fmn+Binding+Site+For+Chain+C'>CC5</scene>, <scene name='pdbsite=CC6:Fad+Binding+Site+For+Chain+C'>CC6</scene>, <scene name='pdbsite=DC5:Fmn+Binding+Site+For+Chain+D'>DC5</scene> and <scene name='pdbsite=DC6:Fad+Binding+Site+For+Chain+D'>DC6</scene>
+
== Structural highlights ==
-
|LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>
+
<table><tr><td colspan='2'>[[1h7w]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H7W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H7W FirstGlance]. <br>
-
|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>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
-
|GENE= DPYD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 Sus scrofa])
+
<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=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr>
-
|DOMAIN=
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1h7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h7w OCA], [https://pdbe.org/1h7w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h7w RCSB], [https://www.ebi.ac.uk/pdbsum/1h7w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h7w ProSAT]</span></td></tr>
-
|RELATEDENTRY=
+
</table>
-
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1h7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h7w OCA], [http://www.ebi.ac.uk/pdbsum/1h7w PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1h7w RCSB]</span>
+
== Function ==
-
}}
+
[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>
-
 
+
== Evolutionary Conservation ==
-
'''DIHYDROPYRIMIDINE DEHYDROGENASE (DPD) FROM PIG'''
+
[[Image:Consurf_key_small.gif|200px|right]]
-
 
+
Check<jmol>
-
 
+
<jmolCheckbox>
-
==Overview==
+
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h7/1h7w_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1h7w ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
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.
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 Structure==
+
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<ref>PMID:11179210</ref>
-
1H7W 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=1H7W OCA].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
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]
+
</div>
-
[[Category: Dihydropyrimidine dehydrogenase (NADP(+))]]
+
<div class="pdbe-citations 1h7w" style="background-color:#fffaf0;"></div>
-
[[Category: Single protein]]
+
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Sus scrofa]]
-
[[Category: Dobritzsch, D.]]
+
[[Category: Dobritzsch D]]
-
[[Category: Lindqvist, Y.]]
+
[[Category: Lindqvist Y]]
-
[[Category: Schnackerz, K D.]]
+
[[Category: Schnackerz KD]]
-
[[Category: Schneider, G.]]
+
[[Category: Schneider G]]
-
[[Category: electron transfer]]
+
-
[[Category: flavin]]
+
-
[[Category: iron-sulfur cluster]]
+
-
[[Category: oxidoreductase]]
+
-
[[Category: pyrimidine catabolism]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:59:37 2008''
+

Current revision

Dihydropyrimidine dehydrogenase (DPD) from pig

PDB ID 1h7w

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1h7w"
Personal tools