1d3g

From Proteopedia

(Difference between revisions)

Revision as of 04:09, 30 August 2017

HUMAN DIHYDROOROTATE DEHYDROGENASE COMPLEXED WITH BREQUINAR ANALOG

Structural highlights

1d3g is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
Related:	1d3h
Activity:	Dihydroorotate oxidase (fumarate), with EC number 1.3.98.1
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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

BACKGROUND: Dihydroorotate dehydrogenase (DHODH) catalyzes the fourth committed step in the de novo biosynthesis of pyrimidines. As rapidly proliferating human T cells have an exceptional requirement for de novo pyrimidine biosynthesis, small molecule DHODH inhibitors constitute an attractive therapeutic approach to autoimmune diseases, immunosuppression, and cancer. Neither the structure of human DHODH nor any member of its family was known. RESULTS: The high-resolution crystal structures of human DHODH in complex with two different inhibitors have been solved. The initial set of phases was obtained using multiwavelength anomalous diffraction phasing with selenomethionine-containing DHODH. The structures have been refined to crystallographic R factors of 16.8% and 16.2% at resolutions of 1. 6 A and 1.8 A for inhibitors related to brequinar and leflunomide, respectively. CONCLUSIONS: Human DHODH has two domains: an alpha/beta-barrel domain containing the active site and an alpha-helical domain that forms the opening of a tunnel leading to the active site. Both inhibitors share a common binding site in this tunnel, and differences in the binding region govern drug sensitivity or resistance. The active site of human DHODH is generally similar to that of the previously reported bacterial active site. The greatest differences are that the catalytic base removing the proton from dihydroorotate is a serine rather than a cysteine, and that packing of the flavin mononucleotide in its binding site is tighter.

Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents.,Liu S, Neidhardt EA, Grossman TH, Ocain T, Clardy J Structure. 2000 Jan 15;8(1):25-33. PMID:10673429^[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
↑ Liu S, Neidhardt EA, Grossman TH, Ocain T, Clardy J. Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents. Structure. 2000 Jan 15;8(1):25-33. PMID:10673429

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1d3g"

@@ Line 1: / Line 1: @@
 ==HUMAN DIHYDROOROTATE DEHYDROGENASE COMPLEXED WITH BREQUINAR ANALOG==
 <StructureSection load='1d3g' size='340' side='right' caption='[[1d3g]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1d3g]] 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=1D3G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1D3G FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1d3g]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D3G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1D3G 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=BRE:2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC+ACID'>BRE</scene>, <scene name='pdbligand=DDQ:DECYLAMINE-N,N-DIMETHYL-N-OXIDE'>DDQ</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]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydroorotate_oxidase_(fumarate) Dihydroorotate oxidase (fumarate)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.98.1 1.3.98.1] </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=1d3g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d3g OCA], [http://pdbe.org/1d3g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1d3g RCSB], [http://www.ebi.ac.uk/pdbsum/1d3g 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=1d3g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d3g OCA], [http://pdbe.org/1d3g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1d3g RCSB], [http://www.ebi.ac.uk/pdbsum/1d3g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1d3g ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
     <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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=1d3g ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 38: / Line 39: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
 [[Category: Clardy, J]]
 [[Category: Grossman, T H]]

1d3g

From Proteopedia

Revision as of 04:09, 30 August 2017

HUMAN DIHYDROOROTATE DEHYDROGENASE COMPLEXED WITH BREQUINAR ANALOG

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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