4orm - Revision history

OCA at 12:41, 1 March 2024

2024-03-01T12:41:51Z

←Older revision		Revision as of 12:41, 1 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4orm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ORM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ORM FirstGlance]. <br>		<table><tr><td colspan='2'>[[4orm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ORM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ORM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2V6:N-[3,5-DIFLUORO-4-(TRIFLUOROMETHYL)PHENYL]-5-METHYL-2-(TRIFLUOROMETHYL)[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-AMINE'>2V6</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>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.07Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2V6:N-[3,5-DIFLUORO-4-(TRIFLUOROMETHYL)PHENYL]-5-METHYL-2-(TRIFLUOROMETHYL)[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-AMINE'>2V6</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=4orm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4orm OCA], [https://pdbe.org/4orm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4orm RCSB], [https://www.ebi.ac.uk/pdbsum/4orm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4orm ProSAT]</span></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=4orm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4orm OCA], [https://pdbe.org/4orm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4orm RCSB], [https://www.ebi.ac.uk/pdbsum/4orm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4orm ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/PYRD_PLAF7 PYRD_PLAF7] Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.		[https://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 is one of the most serious global infectious diseases. The pyrimidine biosynthetic enzyme Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) is an important target for antimalarial chemotherapy. We describe a detailed analysis of protein-ligand interactions between DHODH and a triazolopyrimidine-based inhibitor series exploring effects of fluorine on affinity and species-selectivity. We show increasing fluorination dramatically increases binding to mammalian DHODHs, leading to a loss of species selectivity. Triazolopyrimidines bind Plasmodium and mammalian DHODHs in overlapping but distinct binding-sites. Key hydrogen-bond and stacking-interactions underlying strong binding to PfDHODH are absent in the mammalian enzymes. Increasing fluorine substitution leads to an increase in the entropic contribution to binding suggesting that strong binding to mammalian DHODH is a consequence of an enhanced hydrophobic effect upon binding to an apolar pocket. We conclude that hydrophobic interactions between fluorine and hydrocarbons provide significant binding energy to protein-ligand interactions. Our studies define the requirements for species selective binding to PfDHODH and show that the triazolopyrimidine scaffold can alternatively be tuned to inhibit human DHODH, an important target for autoimmune diseases.
-
-	Fluorine modulates species selectivity in the triazolopyrimidine class of Plasmodium falciparum dihydroorotate dehydrogenase inhibitors.,Deng X, Kokkonda S, El Mazouni F, White J, Burrows JN, Kaminsky W, Charman SA, Matthews D, Rathod PK, Phillips MA J Med Chem. 2014 May 7. PMID:24801997<ref>PMID:24801997</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4orm" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Dihydroorotate dehydrogenase 3D structures\|Dihydroorotate dehydrogenase 3D structures]]		*[[Dihydroorotate dehydrogenase 3D structures\|Dihydroorotate dehydrogenase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 07:42, 25 January 2023

2023-01-25T07:42:29Z

←Older revision		Revision as of 07:42, 25 January 2023
Line 1:		Line 1:

	==Crystal structure of Plasmodium falciparum dihydroorotate dehydrogenase bound with Inhibitor DSM338 (N-[3,5-difluoro-4-(trifluoromethyl)phenyl]-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine)==		==Crystal structure of Plasmodium falciparum dihydroorotate dehydrogenase bound with Inhibitor DSM338 (N-[3,5-difluoro-4-(trifluoromethyl)phenyl]-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine)==
-	<StructureSection load='4orm' size='340' side='right' caption='[[4orm]], [[Resolution\|resolution]] 2.07Å' scene=''>	+	<StructureSection load='4orm' size='340' side='right'caption='[[4orm]], [[Resolution\|resolution]] 2.07Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4orm]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Plaf7 Plaf7~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ORM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4ORM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4orm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ORM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ORM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2V6:N-[3,5-DIFLUORO-4-(TRIFLUOROMETHYL)PHENYL]-5-METHYL-2-(TRIFLUOROMETHYL)[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-AMINE'>2V6</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>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2V6:N-[3,5-DIFLUORO-4-(TRIFLUOROMETHYL)PHENYL]-5-METHYL-2-(TRIFLUOROMETHYL)[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-AMINE'>2V6</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4oqv\|4oqv]], [[4ori\|4ori]]</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=4orm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4orm OCA], [https://pdbe.org/4orm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4orm RCSB], [https://www.ebi.ac.uk/pdbsum/4orm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4orm ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">dihydroorotate dehydrogenase, PFF0160c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</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=4orm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4orm OCA], [~~http~~://pdbe.org/4orm PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4orm RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4orm PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4orm ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PYRD_PLAF7 PYRD_PLAF7]] Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.	+	[https://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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4orm" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4orm" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dihydroorotate dehydrogenase 3D structures\|Dihydroorotate dehydrogenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Plaf7~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Deng, X~~]]	+	[[Category: Plasmodium falciparum 3D7]]
-	[[Category: ~~Phillips, M A~~]]	+	[[Category: Deng X]]
-	[[Category: ~~Alpha/beta barrel]]~~	+	[[Category: Phillips MA]]
-	~~[[Category: Fmn]]~~	+
-	~~[[Category: Mitochondrial membrane]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]	+

OCA at 22:36, 15 November 2017

2017-11-15T22:36:00Z

←Older revision		Revision as of 22:36, 15 November 2017
Line 3:		Line 3:
	<StructureSection load='4orm' size='340' side='right' caption='[[4orm]], [[Resolution\|resolution]] 2.07Å' scene=''>		<StructureSection load='4orm' size='340' side='right' caption='[[4orm]], [[Resolution\|resolution]] 2.07Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4orm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ORM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ORM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4orm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ORM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ORM FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2V6:N-[3,5-DIFLUORO-4-(TRIFLUOROMETHYL)PHENYL]-5-METHYL-2-(TRIFLUOROMETHYL)[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-AMINE'>2V6</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>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2V6:N-[3,5-DIFLUORO-4-(TRIFLUOROMETHYL)PHENYL]-5-METHYL-2-(TRIFLUOROMETHYL)[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-AMINE'>2V6</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4oqv\|4oqv]], [[4ori\|4ori]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4oqv\|4oqv]], [[4ori\|4ori]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">dihydroorotate dehydrogenase, PFF0160c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</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='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=4orm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4orm OCA], [http://pdbe.org/4orm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4orm RCSB], [http://www.ebi.ac.uk/pdbsum/4orm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4orm ProSAT]</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=4orm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4orm OCA], [http://pdbe.org/4orm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4orm RCSB], [http://www.ebi.ac.uk/pdbsum/4orm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4orm ProSAT]</span></td></tr>
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4orm" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4orm" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Dihydroorotate dehydrogenase\|Dihydroorotate dehydrogenase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Plaf7]]
	[[Category: Deng, X]]		[[Category: Deng, X]]
	[[Category: Phillips, M A]]		[[Category: Phillips, M A]]

OCA at 01:45, 5 August 2016

2016-08-05T01:45:47Z

←Older revision		Revision as of 01:45, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of Plasmodium falciparum dihydroorotate dehydrogenase bound with Inhibitor DSM338 (N-[3,5-difluoro-4-(trifluoromethyl)phenyl]-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine)==		==Crystal structure of Plasmodium falciparum dihydroorotate dehydrogenase bound with Inhibitor DSM338 (N-[3,5-difluoro-4-(trifluoromethyl)phenyl]-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine)==
	<StructureSection load='4orm' size='340' side='right' caption='[[4orm]], [[Resolution\|resolution]] 2.07Å' scene=''>		<StructureSection load='4orm' size='340' side='right' caption='[[4orm]], [[Resolution\|resolution]] 2.07Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4oqv\|4oqv]], [[4ori\|4ori]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4oqv\|4oqv]], [[4ori\|4ori]]</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='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=4orm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4orm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4orm RCSB], [http://www.ebi.ac.uk/pdbsum/4orm PDBsum]</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=4orm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4orm OCA], [http://pdbe.org/4orm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4orm RCSB], [http://www.ebi.ac.uk/pdbsum/4orm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4orm ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4orm" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dihydroorotate dehydrogenase\|Dihydroorotate dehydrogenase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 21:43, 24 December 2014

2014-12-24T21:43:04Z

←Older revision		Revision as of 21:43, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4orm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ORM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ORM FirstGlance]. <br>		<table><tr><td colspan='2'>[[4orm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ORM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ORM FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2V6:N-[3,5-DIFLUORO-4-(TRIFLUOROMETHYL)PHENYL]-5-METHYL-2-(TRIFLUOROMETHYL)[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-AMINE'>2V6</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><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2V6:N-[3,5-DIFLUORO-4-(TRIFLUOROMETHYL)PHENYL]-5-METHYL-2-(TRIFLUOROMETHYL)[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-AMINE'>2V6</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><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4oqv\|4oqv]], [[4ori\|4ori]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4oqv\|4oqv]], [[4ori\|4ori]]</td></tr>
-	<tr><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='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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4orm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4orm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4orm RCSB], [http://www.ebi.ac.uk/pdbsum/4orm PDBsum]</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=4orm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4orm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4orm RCSB], [http://www.ebi.ac.uk/pdbsum/4orm PDBsum]</span></td></tr>
-	<table>	+	</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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Deng, X.]]	+	[[Category: Deng, X]]
-	[[Category: Phillips, M A.]]	+	[[Category: Phillips, M A]]
	[[Category: Alpha/beta barrel]]		[[Category: Alpha/beta barrel]]
	[[Category: Fmn]]		[[Category: Fmn]]

OCA at 06:12, 9 July 2014

2014-07-09T06:12:33Z

←Older revision		Revision as of 06:12, 9 July 2014
Line 14:		Line 14:
	Fluorine modulates species selectivity in the triazolopyrimidine class of Plasmodium falciparum dihydroorotate dehydrogenase inhibitors.,Deng X, Kokkonda S, El Mazouni F, White J, Burrows JN, Kaminsky W, Charman SA, Matthews D, Rathod PK, Phillips MA J Med Chem. 2014 May 7. PMID:24801997<ref>PMID:24801997</ref>		Fluorine modulates species selectivity in the triazolopyrimidine class of Plasmodium falciparum dihydroorotate dehydrogenase inhibitors.,Deng X, Kokkonda S, El Mazouni F, White J, Burrows JN, Kaminsky W, Charman SA, Matthews D, Rathod PK, Phillips MA J Med Chem. 2014 May 7. PMID:24801997<ref>PMID:24801997</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, a database of the U.S. National Library of Medicine.<br>	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
	== References ==		== References ==

OCA at 05:05, 4 June 2014

2014-06-04T05:05:45Z

←Older revision		Revision as of 05:05, 4 June 2014
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal structure of Plasmodium falciparum dihydroorotate dehydrogenase bound with Inhibitor DSM338 (N-[3,5-difluoro-4-(trifluoromethyl)phenyl]-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine)==
		+	<StructureSection load='4orm' size='340' side='right' caption='[[4orm]], [[Resolution\|resolution]] 2.07Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4orm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ORM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ORM FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2V6:N-[3,5-DIFLUORO-4-(TRIFLUOROMETHYL)PHENYL]-5-METHYL-2-(TRIFLUOROMETHYL)[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-AMINE'>2V6</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><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4oqv\|4oqv]], [[4ori\|4ori]]</td></tr>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4orm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4orm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4orm RCSB], [http://www.ebi.ac.uk/pdbsum/4orm PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Malaria is one of the most serious global infectious diseases. The pyrimidine biosynthetic enzyme Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) is an important target for antimalarial chemotherapy. We describe a detailed analysis of protein-ligand interactions between DHODH and a triazolopyrimidine-based inhibitor series exploring effects of fluorine on affinity and species-selectivity. We show increasing fluorination dramatically increases binding to mammalian DHODHs, leading to a loss of species selectivity. Triazolopyrimidines bind Plasmodium and mammalian DHODHs in overlapping but distinct binding-sites. Key hydrogen-bond and stacking-interactions underlying strong binding to PfDHODH are absent in the mammalian enzymes. Increasing fluorine substitution leads to an increase in the entropic contribution to binding suggesting that strong binding to mammalian DHODH is a consequence of an enhanced hydrophobic effect upon binding to an apolar pocket. We conclude that hydrophobic interactions between fluorine and hydrocarbons provide significant binding energy to protein-ligand interactions. Our studies define the requirements for species selective binding to PfDHODH and show that the triazolopyrimidine scaffold can alternatively be tuned to inhibit human DHODH, an important target for autoimmune diseases.

-	~~The entry 4orm is ON HOLD until Paper Publication~~	+	Fluorine modulates species selectivity in the triazolopyrimidine class of Plasmodium falciparum dihydroorotate dehydrogenase inhibitors.,Deng X, Kokkonda S, El Mazouni F, White J, Burrows JN, Kaminsky W, Charman SA, Matthews D, Rathod PK, Phillips MA J Med Chem. 2014 May 7. PMID:24801997<ref>PMID:24801997</ref>

-	~~Authors~~: Deng, X., Phillips, M.A.	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Crystal structure of Plasmodium falciparum dihydroorotate dehydrogenase bound with Inhibitor DSM338 (N-~~[~~3,5-difluoro-4-(trifluoromethyl)phenyl~~]~~-5-methyl-2-(trifluoromethyl)~~[~~1,2,4~~]~~triazolo~~[~~1,5~~-a]~~pyrimidin-7-amine)~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Deng, X.]]
		+	[[Category: Phillips, M A.]]
		+	[[Category: Alpha/beta barrel]]
		+	[[Category: Fmn]]
		+	[[Category: Mitochondrial membrane]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

OCA at 12:20, 12 March 2014

2014-03-12T12:20:02Z

←Older revision		Revision as of 12:20, 12 March 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4orm is ON HOLD	+	The entry 4orm is ON HOLD until Paper Publication

	Authors: Deng, X., Phillips, M.A.		Authors: Deng, X., Phillips, M.A.

	Description: Crystal structure of Plasmodium falciparum dihydroorotate dehydrogenase bound with Inhibitor DSM338 (N-[3,5-difluoro-4-(trifluoromethyl)phenyl]-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine)		Description: Crystal structure of Plasmodium falciparum dihydroorotate dehydrogenase bound with Inhibitor DSM338 (N-[3,5-difluoro-4-(trifluoromethyl)phenyl]-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine)

OCA at 16:49, 3 March 2014

2014-03-03T16:49:59Z

←Older revision		Revision as of 16:49, 3 March 2014
Line 3:		Line 3:
	The entry 4orm is ON HOLD		The entry 4orm is ON HOLD

-	Authors: Deng, X, Phillips, MA	+	Authors: Deng, X., Phillips, M.A.

-	Description: Crystal structure of Plasmodium falciparum dihydroorotate dehydrogenase bound with Inhibitor DSM338	+	Description: Crystal structure of Plasmodium falciparum dihydroorotate dehydrogenase bound with Inhibitor DSM338 (N-[3,5-difluoro-4-(trifluoromethyl)phenyl]-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine)

OCA: Protected "4orm" [edit=sysop:move=sysop]

2014-02-19T16:21:08Z

Protected "4orm" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:21, 19 February 2014