3zws

From Proteopedia

(Difference between revisions)

Revision as of 10:27, 4 August 2016

Structure of Human Dihydroorotate Dehydrogenase with a Bound Inhibitor

Structural highlights

3zws is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
Related:	1d3h, 2wv8, 2b0m, 1d3g, 2bxv, 3zwt
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PYRD_HUMAN] Defects in DHODH are the cause of postaxial acrofacial dysostosis (POADS) [MIM:263750]; also known as Miller syndrome. POADS is characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. POADS is a very rare disorder: only 2 multiplex families, each consisting of 2 affected siblings born to unaffected, nonconsanguineous parents, have been described among a total of around 30 reported cases.^[1]

Function

[PYRD_HUMAN] Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.

Publication Abstract from PubMed

The de novo pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase is an emerging drug target for the treatment of malaria. In this context a key property of Plasmodium falciparum DHODH (PfDHODH) is that it can be selectively inhibited over its human homologue (HsDHODH). However, HsDHODH is also a validated drug target for autoimmune diseases such as arthritis. Here a series of novel inhibitors is described that includes compounds that switch specificity between the two enzymes as a result of small alterations in chemical structure. Structure-activity relationship (SAR), crystallography, docking, and mutagenesis studies are used to examine the binding modes of the compounds within the two enzymes and to reveal structural changes induced by inhibitor binding. Within this series, compounds with therapeutically relevant HsDHODH activity are described and their binding modes characterized using X-ray crystallography, which reveals a novel conformational shift within the inhibitor binding site.

Factors Influencing the Specificity of Inhibitor Binding to the Human and Malaria Parasite Dihydroorotate Dehydrogenases.,Bedingfield PT, Cowen D, Acklam P, Cunningham F, Parsons MR, McConkey GA, Fishwick CW, Johnson AP J Med Chem. 2012 Jun 15. PMID:22621375^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet. 2010 Jan;42(1):30-5. doi: 10.1038/ng.499. Epub 2009 Nov 13. PMID:19915526 doi:10.1038/ng.499
↑ Bedingfield PT, Cowen D, Acklam P, Cunningham F, Parsons MR, McConkey GA, Fishwick CW, Johnson AP. Factors Influencing the Specificity of Inhibitor Binding to the Human and Malaria Parasite Dihydroorotate Dehydrogenases. J Med Chem. 2012 Jun 15. PMID:22621375 doi:10.1021/jm300157n

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3zws"

Categories: Human | Acklam, P A | Parsons, M R | Oxidoreductase

@@ Line 1: / Line 1: @@
 ==Structure of Human Dihydroorotate Dehydrogenase with a Bound Inhibitor==
 <StructureSection load='3zws' size='340' side='right' caption='[[3zws]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3zws]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZWS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZWS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3zws]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZWS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZWS FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=AVQ:2-[(2,5-DICHLOROBENZYL)SULFANYL]-5-METHYL[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-OL'>AVQ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1d3h|1d3h]], [[2wv8|2wv8]], [[2b0m|2b0m]], [[1d3g|1d3g]], [[2bxv|2bxv]], [[3zwt|3zwt]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3zws FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zws OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zws RCSB], [http://www.ebi.ac.uk/pdbsum/3zws PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3zws FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zws OCA], [http://pdbe.org/3zws PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zws RCSB], [http://www.ebi.ac.uk/pdbsum/3zws PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zws ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3zws" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 26: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Acklam, P A]]
 [[Category: Parsons, M R]]
 [[Category: Oxidoreductase]]

3zws

From Proteopedia

Revision as of 10:27, 4 August 2016

Structure of Human Dihydroorotate Dehydrogenase with a Bound Inhibitor

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox