5mvd - Revision history

OCA at 17:51, 8 November 2023

OCA — Wed, 08 Nov 2023 17:51:19 GMT

←Older revision		Revision as of 17:51, 8 November 2023
Line 3:		Line 3:
	<StructureSection load='5mvd' size='340' side='right'caption='[[5mvd]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='5mvd' size='340' side='right'caption='[[5mvd]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mvd]] 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=5MVD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5MVD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mvd]] 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=5MVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MVD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene>, <scene name='pdbligand=U91:1,5-DIMETHYL-3-OXIDANYL-~{N}-[2,3,5,6-TETRAKIS(FLUORANYL)-4-PHENYL-PHENYL]PYRAZOLE-4-CARBOXAMIDE'>U91</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]] 1.95Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHODH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene>, <scene name='pdbligand=U91:1,5-DIMETHYL-3-OXIDANYL-~{N}-[2,3,5,6-TETRAKIS(FLUORANYL)-4-PHENYL-PHENYL]PYRAZOLE-4-CARBOXAMIDE'>U91</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'>[https://proteopedia.org/fgij/fg.htm?mol=5mvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mvd OCA], [https://pdbe.org/5mvd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mvd RCSB], [https://www.ebi.ac.uk/pdbsum/5mvd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mvd ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5mvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mvd OCA], [~~http~~://pdbe.org/5mvd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5mvd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5mvd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5mvd ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/PYRD_HUMAN PYRD_HUMAN]] Defects in DHODH are the cause of postaxial acrofacial dysostosis (POADS) [MIM:[~~http~~://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>	+	[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 ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PYRD_HUMAN PYRD_HUMAN]] Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.	+	[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 29:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Al-Kadaraghi, S]]	+	[[Category: Al-Kadaraghi S]]
-	[[Category: Andersson, M]]	+	[[Category: Andersson M]]
-	[[Category: Boschi, D]]	+	[[Category: Boschi D]]
-	[[Category: Friemann, R]]	+	[[Category: Friemann R]]
-	[[Category: Goyal, P]]	+	[[Category: Goyal P]]
-	[[Category: Lolli, M]]	+	[[Category: Lolli M]]
-	[[Category: Moritzer~~, A C~~]]	+	[[Category: Moritzer AC]]
-	[[Category: Pippione~~, A C~~]]	+	[[Category: Pippione AC]]
-	[[Category: Sainas, S]]	+	[[Category: Sainas S]]
-	~~[[Category: Dhodh]]~~	+
-	~~[[Category: Human dhodh]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 07:30, 19 August 2020

OCA — Wed, 19 Aug 2020 07:30:04 GMT

←Older revision		Revision as of 07:30, 19 August 2020
Line 1:		Line 1:

	==Crystal structure of potent human Dihydroorotate Dehydrogenase inhibitors based on hydroxylated azole scaffolds==		==Crystal structure of potent human Dihydroorotate Dehydrogenase inhibitors based on hydroxylated azole scaffolds==
-	<StructureSection load='5mvd' size='340' side='right' caption='[[5mvd]], [[Resolution\|resolution]] 1.95Å' scene=''>	+	<StructureSection load='5mvd' size='340' side='right'caption='[[5mvd]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mvd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MVD OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5MVD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mvd]] 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=5MVD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MVD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene>, <scene name='pdbligand=U91:1,5-DIMETHYL-3-OXIDANYL-~{N}-[2,3,5,6-TETRAKIS(FLUORANYL)-4-PHENYL-PHENYL]PYRAZOLE-4-CARBOXAMIDE'>U91</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene>, <scene name='pdbligand=U91:1,5-DIMETHYL-3-OXIDANYL-~{N}-[2,3,5,6-TETRAKIS(FLUORANYL)-4-PHENYL-PHENYL]PYRAZOLE-4-CARBOXAMIDE'>U91</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHODH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5mvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mvd OCA], [http://pdbe.org/5mvd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mvd RCSB], [http://www.ebi.ac.uk/pdbsum/5mvd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mvd ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mvd OCA], [http://pdbe.org/5mvd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mvd RCSB], [http://www.ebi.ac.uk/pdbsum/5mvd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mvd ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 5mvd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5mvd" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dihydroorotate dehydrogenase 3D structures\|Dihydroorotate dehydrogenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Al-Kadaraghi, S]]		[[Category: Al-Kadaraghi, S]]
	[[Category: Andersson, M]]		[[Category: Andersson, M]]

OCA at 16:49, 9 March 2017

OCA — Thu, 09 Mar 2017 16:49:34 GMT

←Older revision		Revision as of 16:49, 9 March 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5mvd is ~~ON HOLD~~	+	==Crystal structure of potent human Dihydroorotate Dehydrogenase inhibitors based on hydroxylated azole scaffolds==
		+	<StructureSection load='5mvd' size='340' side='right' caption='[[5mvd]], [[Resolution\|resolution]] 1.95Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5mvd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MVD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MVD FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=ORO:OROTIC+ACID'>ORO</scene>, <scene name='pdbligand=U91:1,5-DIMETHYL-3-OXIDANYL-~{N}-[2,3,5,6-TETRAKIS(FLUORANYL)-4-PHENYL-PHENYL]PYRAZOLE-4-CARBOXAMIDE'>U91</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=5mvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mvd OCA], [http://pdbe.org/5mvd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mvd RCSB], [http://www.ebi.ac.uk/pdbsum/5mvd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mvd ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/PYRD_HUMAN PYRD_HUMAN]] Defects in DHODH are the cause of postaxial acrofacial dysostosis (POADS) [MIM:[http://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 ==
		+	[[http://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 ==
		+	A new generation of potent hDHODH inhibitors designed by a scaffold-hopping replacement of the quinolinecarboxylate moiety of brequinar, one of the most potent known hDHODH inhibitors, is presented here. Their general structure is characterized by a biphenyl moiety joined through an amide bridge with an acidic hydroxyazole scaffold (hydroxylated thiadiazole, pyrazole and triazole). Molecular modelling suggested that these structures should adopt a brequinar-like binding mode involving interactions with subsites 1, 2 and 4 of the hDHODH binding site. Initially, the inhibitory activity of the compounds was studied on recombinant hDHODH. The most potent compound of the series in the enzymatic assays was the thiadiazole analogue 4 (IC50 16 nM). The activity was found to be dependent on the fluoro substitution pattern at the biphenyl moiety as well as on the choice/substitution of the heterocyclic ring. Structure determination of hDHODH co-crystallized with one representative compound from each series (4, 5 and 6) confirmed the brequinar-like binding mode as suggested by modelling. The specificity of the observed effects of the compound series was tested in cell-based assays for antiproliferation activity using Jurkat cells and PHA-stimulated PBMC. These tests were also verified by addition of exogenous uridine to the culture medium. In particular, the triazole analogue 6 (IC50 against hDHODH: 45 nM) exerted potent in vitro antiproliferative and immunosuppressive activity without affecting cell survival.

-	~~Authors: Goyal~~, P., ~~Andersson~~, M., ~~Moritzer~~, A.C., ~~Sainas~~, S., ~~Pippione~~, ~~A.C.~~, ~~Boschi~~, D., Al-Kadaraghi, S.	+	Design, synthesis, biological evaluation and X-ray structural studies of potent human dihydroorotate dehydrogenase inhibitors based on hydroxylated azole scaffolds.,Sainas S, Pippione AC, Giorgis M, Lupino E, Goyal P, Ramondetti C, Buccinna B, Piccinini M, Braga RC, Andrade CH, Andersson M, Moritzer AC, Friemann R, Mensa S, Al-Kadaraghi S, Boschi D, Lolli ML Eur J Med Chem. 2017 Mar 31;129:287-302. doi: 10.1016/j.ejmech.2017.02.017. Epub , 2017 Feb 14. PMID:28235702<ref>PMID:28235702</ref>

-	~~Description: Crystal structure~~ of ~~potent human Dihydroorotate Dehydrogenase inhibitors based on hydroxylated azole scaffolds~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Sainas, S]]~~	+	<div class="pdbe-citations 5mvd" style="background-color:#fffaf0;"></div>
-	~~[[Category: Goyal, P]]~~	+	== References ==
-	~~[[Category: Pippione, A.C]]~~	+	<references/>
-	~~[[Category: Andersson, M]]~~	+	__TOC__
		+	</StructureSection>
	[[Category: Al-Kadaraghi, S]]		[[Category: Al-Kadaraghi, S]]
		+	[[Category: Andersson, M]]
	[[Category: Boschi, D]]		[[Category: Boschi, D]]
-	[[Category: Moritzer, A.C]]	+	[[Category: Friemann, R]]
		+	[[Category: Goyal, P]]
		+	[[Category: Lolli, M]]
		+	[[Category: Moritzer, A C]]
		+	[[Category: Pippione, A C]]
		+	[[Category: Sainas, S]]
		+	[[Category: Dhodh]]
		+	[[Category: Human dhodh]]
		+	[[Category: Oxidoreductase]]

OCA: Protected "5mvd" [edit=sysop:move=sysop]

OCA — Wed, 25 Jan 2017 20:37:43 GMT

Protected "5mvd" [edit=sysop:move=sysop]

←Older revision

Revision as of 20:37, 25 January 2017

OCA: New page: '''Unreleased structure''' The entry 5mvd is ON HOLD Authors: Goyal, P., Andersson, M., Moritzer, A.C., Sainas, S., Pippione, A.C., Boschi, D., Al-Kadaraghi, S. Description: Crystal st...

OCA — Wed, 25 Jan 2017 20:37:42 GMT

New page: '''Unreleased structure''' The entry 5mvd is ON HOLD Authors: Goyal, P., Andersson, M., Moritzer, A.C., Sainas, S., Pippione, A.C., Boschi, D., Al-Kadaraghi, S. Description: Crystal st...

New page

'''Unreleased structure'''

The entry 5mvd is ON HOLD

Authors: Goyal, P., Andersson, M., Moritzer, A.C., Sainas, S., Pippione, A.C., Boschi, D., Al-Kadaraghi, S.

Description: Crystal structure of potent human Dihydroorotate Dehydrogenase inhibitors based on hydroxylated azole scaffolds
[[Category: Unreleased Structures]]
[[Category: Sainas, S]]
[[Category: Goyal, P]]
[[Category: Pippione, A.C]]
[[Category: Andersson, M]]
[[Category: Al-Kadaraghi, S]]
[[Category: Boschi, D]]
[[Category: Moritzer, A.C]]