OCA at 08:08, 22 May 2024

OCA — Wed, 22 May 2024 08:08:12 GMT

←Older revision		Revision as of 08:08, 22 May 2024
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-	'''Unreleased structure'''

-	~~The entry~~ 8yhr is ~~ON HOLD until Paper~~ Publication	+	==DHODH in complex with furocoumavirin==
		+	<StructureSection load='8yhr' size='340' side='right'caption='[[8yhr]], [[Resolution\|resolution]] 1.70Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8yhr]] 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=8YHR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8YHR 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]] 1.7Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1LYU:4-methyl-8-[(S)-oxidanyl(phenyl)methyl]-9-phenyl-furo[2,3-h]chromen-2-one'>A1LYU</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</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=8yhr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8yhr OCA], [https://pdbe.org/8yhr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8yhr RCSB], [https://www.ebi.ac.uk/pdbsum/8yhr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8yhr 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.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Natural products are important sources of seed compounds for drug discovery. However, it has become difficult in recent years to discover new compounds with valuable pharmacological activities. On the other hand, among the vast number of natural products that have been isolated so far, a considerable number of compounds with specific biological activities are thought to be overlooked in screening that uses biological activity as an index. Therefore, it is conceivable that such overlooked useful compounds may be found by screening compound libraries that have been amassed previously through specific assays. Previously, NPD723, a member of the Natural Products Depository library comprised of a mixture of natural and non-natural products developed at RIKEN, and its metabolite H-006 were found to inhibit growth of various cancer cells at low nanomolar half-maximal inhibitory concentration. Subsequent analysis revealed that H-006 strongly inhibited human dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme in the de novo pyrimidine biosynthetic pathway. Here, we elucidated the crystal structure of the DHODH-flavin mononucleotide-orotic acid-H-006 complex at 1.7 A resolution to determine that furocoumavirin, the S-enantiomer of H-006, was the actual inhibitor. The overall mode of interaction of furocoumavirin with the inhibitor binding pocket was similar to that described for previously reported tight-binding inhibitors. However, the structural information together with kinetic characterizations of site-specific mutants identified key unique features that are considered to contribute to the sub-nanomolar inhibition of DHODH by furocoumavirin. Our finding identified new chemical features that could improve the design of human DHODH inhibitors.

-	~~Authors~~:	+	Structural and Functional Analyses of Inhibition of Human Dihydroorotate Dehydrogenase by Antiviral Furocoumavirin.,Nakahara M, Watanabe S, Sato M, Okumura H, Kawatani M, Osada H, Hara K, Hashimoto H, Watanabe K Biochemistry. 2024 May 21;63(10):1241-1245. doi: 10.1021/acs.biochem.4c00120. , Epub 2024 May 9. PMID:38724483<ref>PMID:38724483</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8yhr" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Hara K]]
		+	[[Category: Hashimoto H]]
		+	[[Category: Nakahara M]]
		+	[[Category: Okumura H]]
		+	[[Category: Osada H]]
		+	[[Category: Sato M]]
		+	[[Category: Watanabe K]]

OCA at 04:40, 3 April 2024

OCA — Wed, 03 Apr 2024 04:40:35 GMT

←Older revision		Revision as of 04:40, 3 April 2024
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8yhr is ON HOLD	+	The entry 8yhr is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8yhr" [edit=sysop:move=sysop]

OCA — Wed, 06 Mar 2024 10:50:09 GMT

Protected "8yhr" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:50, 6 March 2024

OCA: New page: '''Unreleased structure''' The entry 8yhr is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 06 Mar 2024 10:50:07 GMT

New page: '''Unreleased structure''' The entry 8yhr is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8yhr is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

8yhr - Revision history

OCA at 08:08, 22 May 2024

OCA at 04:40, 3 April 2024

OCA: Protected "8yhr" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8yhr is ON HOLD Authors: Description: Category: Unreleased Structures