3kvk

From Proteopedia

Crystal structure of human dihydroorotate dehydrogenase (DHODH) with amino-benzoic acid inhibitor 641 at 2.05A resolution

PDB ID 3kvk

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Structural highlights

3kvk is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.05Å
Ligands:	, , , ,
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

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^[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
↑ McLean LR, Zhang Y, Degnen W, Peppard J, Cabel D, Zou C, Tsay JT, Subramaniam A, Vaz RJ, Li Y. Discovery of novel inhibitors for DHODH via virtual screening and X-ray crystallographic structures. Bioorg Med Chem Lett. 2010 Mar 15;20(6):1981-4. Epub 2010 Jan 25. PMID:20153645 doi:10.1016/j.bmcl.2010.01.115