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.

2wv8

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 14:05, 25 December 2019

Complex of human dihydroorotate dehydrogenase with the inhibitor 221290

Structural highlights

2wv8 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, 2b0m, 1d3g, 2bxv
Activity:	Dihydroorotate dehydrogenase (quinone), with EC number 1.3.5.2
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

A strategy that combines virtual screening and structure-guided selection of fragments was used to identify three unexplored classes of human DHODH inhibitor compounds: 4-hydroxycoumarins, fenamic acids, and N-(alkylcarbonyl)anthranilic acids. Structure-guided selection of fragments targeting the inner subsite of the DHODH ubiquinone binding site made these findings possible with screening of fewer than 300 fragments in a DHODH assay. Fragments from the three inhibitor classes identified were subsequently chemically expanded to target an additional subsite of hydrophobic character. All three classes were found to exhibit distinct structure-activity relationships upon expansion. The novel N-(alkylcarbonyl)anthranilic acid class shows the most promising potency against human DHODH, with IC(50) values in the low nanomolar range. The structure of human DHODH in complex with an inhibitor of this class is presented.

Inhibition of human DHODH by 4-hydroxycoumarins, fenamic acids, and N-(alkylcarbonyl)anthranilic acids identified by structure-guided fragment selection.,Fritzson I, Svensson B, Al-Karadaghi S, Walse B, Wellmar U, Nilsson UJ, da Graca Thrige D, Jonsson S ChemMedChem. 2010 Apr 6;5(4):608-17. PMID:20183850^[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
↑ Fritzson I, Svensson B, Al-Karadaghi S, Walse B, Wellmar U, Nilsson UJ, da Graca Thrige D, Jonsson S. Inhibition of human DHODH by 4-hydroxycoumarins, fenamic acids, and N-(alkylcarbonyl)anthranilic acids identified by structure-guided fragment selection. ChemMedChem. 2010 Apr 6;5(4):608-17. PMID:20183850 doi:10.1002/cmdc.200900454

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/2wv8"

@@ Line 1: / Line 1: @@
 ==Complex of human dihydroorotate dehydrogenase with the inhibitor 221290==
-<StructureSection load='2wv8' size='340' side='right' caption='[[2wv8]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+<StructureSection load='2wv8' size='340' side='right'caption='[[2wv8]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2wv8]] 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=2WV8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WV8 FirstGlance]. <br>
@@ Line 32: / Line 32: @@
 </div>
 <div class="pdbe-citations 2wv8" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Dihydroorotate dehydrogenase 3D structures|Dihydroorotate dehydrogenase 3D structures]]
 == References ==
 <references/>
@@ Line 37: / Line 40: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Al-Karadaghi, S]]
 [[Category: Dahlberg, L]]

2wv8

From Proteopedia

Revision as of 14:05, 25 December 2019

Complex of human dihydroorotate dehydrogenase with the inhibitor 221290

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox