3kvm: Difference between revisions
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New page: '''Unreleased structure''' The entry 3kvm is ON HOLD Authors: L.MCLEAN, Y.ZHANG Description: CRYSTAL STRUCTURE OF HUMAN DIHYDROOROTATE DEHYDROGENASE (DHODH) WITH AMINO-BENZOIC ACID INH... |
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==Crystal structure of human dihydroorotate dehydrogenase (DHODH) with amino-benzoic acid inhibitor 951 at 2.00A resolution== | |||
<StructureSection load='3kvm' size='340' side='right'caption='[[3kvm]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3kvm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KVM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KVM FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=951:2-[(2E)-2-{[5-(2-CHLOROPHENYL)FURAN-2-YL]METHYLIDENE}HYDRAZINO]BENZOIC+ACID'>951</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DET:UNDECYLAMINE-N,N-DIMETHYL-N-OXIDE'>DET</scene>, <scene name='pdbligand=DOR:(4S)-2,6-DIOXOHEXAHYDROPYRIMIDINE-4-CARBOXYLIC+ACID'>DOR</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3kvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kvm OCA], [https://pdbe.org/3kvm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kvm RCSB], [https://www.ebi.ac.uk/pdbsum/3kvm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kvm ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/PYRD_HUMAN PYRD_HUMAN] Defects in DHODH are the cause of postaxial acrofacial dysostosis (POADS) [MIM:[https://omim.org/entry/263750 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.<ref>PMID:19915526</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PYRD_HUMAN PYRD_HUMAN] Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kv/3kvm_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=3kvm ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Amino-benzoic acid derivatives 1-4 were found to be inhibitors for DHODH by virtual screening, biochemical, and X-ray crystallographic studies. X-ray structures showed that 1 and 2 bind to DHODH as predicted by virtual screening, but 3 and 4 were found to be structurally different from the corresponding compounds initially identified by virtual screening. | |||
Discovery of novel inhibitors for DHODH via virtual screening and X-ray crystallographic structures.,McLean LR, Zhang Y, Degnen W, Peppard J, Cabel D, Zou C, Tsay JT, Subramaniam A, Vaz RJ, Li Y Bioorg Med Chem Lett. 2010 Mar 15;20(6):1981-4. Epub 2010 Jan 25. PMID:20153645<ref>PMID:20153645</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3kvm" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Dihydroorotate dehydrogenase 3D structures|Dihydroorotate dehydrogenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: McLean L]] | |||
[[Category: Zhang Y]] | |||
Latest revision as of 08:25, 6 September 2023
Crystal structure of human dihydroorotate dehydrogenase (DHODH) with amino-benzoic acid inhibitor 951 at 2.00A resolution
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