OCA at 19:57, 19 September 2018

2018-09-19T19:57:05Z

←Older revision		Revision as of 19:57, 19 September 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6gjg is ~~ON HOLD until Paper~~ Publication	+	==Plasmodium falciparum dihydroorotate dehydrogenase DHODH in complex with 3,6-dimethyl-N-(4-(trifluoromethyl)phenyl)-(1,2)oxazolo(5,4-d)pyrimidin-4-amine==
		+	<StructureSection load='6gjg' size='340' side='right' caption='[[6gjg]], [[Resolution\|resolution]] 1.99Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6gjg]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GJG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GJG FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F1T:3,6-dimethyl-~{N}-[4-(trifluoromethyl)phenyl]-[1,2]oxazolo[5,4-d]pyrimidin-4-amine'>F1T</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydroorotate_dehydrogenase_(quinone) Dihydroorotate dehydrogenase (quinone)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.5.2 1.3.5.2] </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=6gjg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gjg OCA], [http://pdbe.org/6gjg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gjg RCSB], [http://www.ebi.ac.uk/pdbsum/6gjg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gjg ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PYRD_PLAF7 PYRD_PLAF7]] Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Malaria kills nearly 0.5 million people yearly and impacts the lives of those living in over 90 countries where it is endemic. The current treatment programs are threatened by increasing drug resistance. Dihydroorotate dehydrogenase (DHODH) is now clinically validated as a target for antimalarial drug discovery as a triazolopyrimidine class inhibitor (DSM265) is currently undergoing clinical development. We discovered a related isoxazolopyrimidine series in a phenotypic screen, later determining that it targeted DHODH. To determine if the isoxazolopyrimidines could yield a drug candidate, we initiated hit-to-lead medicinal chemistry. Several potent analogues were identified, including a compound that showed in vivo antimalarial activity. The isoxazolopyrimidines were more rapidly metabolized than their triazolopyrimidine counterparts, and the pharmacokinetic data were not consistent with the goal of a single-dose treatment for malaria.

-	~~Authors~~:	+	Isoxazolopyrimidine-Based Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase with Antimalarial Activity.,Kokkonda S, El Mazouni F, White KL, White J, Shackleford DM, Lafuente-Monasterio MJ, Rowland P, Manjalanagara K, Joseph JT, Garcia-Perez A, Fernandez J, Gamo FJ, Waterson D, Burrows JN, Palmer MJ, Charman SA, Rathod PK, Phillips MA ACS Omega. 2018 Aug 31;3(8):9227-9240. doi: 10.1021/acsomega.8b01573. Epub 2018, Aug 15. PMID:30197997<ref>PMID:30197997</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6gjg" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Rowland, P]]
		+	[[Category: Dhodh]]
		+	[[Category: Enzyme]]
		+	[[Category: Flavoprotein]]

OCA: Protected "6gjg" [edit=sysop:move=sysop]

2018-05-23T06:11:54Z

Protected "6gjg" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:11, 23 May 2018

OCA: New page: '''Unreleased structure''' The entry 6gjg is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

2018-05-23T06:11:53Z

New page: '''Unreleased structure''' The entry 6gjg is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6gjg is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]

6gjg - Revision history

OCA at 19:57, 19 September 2018

OCA: Protected "6gjg" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6gjg is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures