6a7e - Revision history

OCA at 09:20, 22 November 2023

OCA — Wed, 22 Nov 2023 09:20:41 GMT

←Older revision		Revision as of 09:20, 22 November 2023
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	<StructureSection load='6a7e' size='340' side='right'caption='[[6a7e]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='6a7e' size='340' side='right'caption='[[6a7e]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6a7e]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A7E OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6A7E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6a7e]] 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=6A7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6A7E FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9QR:5-(4-{3-[(2,4-diamino-6-ethylpyrimidin-5-yl)oxy]propoxy}phenyl)-6-ethylpyrimidine-2,4-diamine'>9QR</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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]] 1.85Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6a7c\|6a7c]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9QR:5-(4-{3-[(2,4-diamino-6-ethylpyrimidin-5-yl)oxy]propoxy}phenyl)-6-ethylpyrimidine-2,4-diamine'>9QR</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </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=6a7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a7e OCA], [https://pdbe.org/6a7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6a7e RCSB], [https://www.ebi.ac.uk/pdbsum/6a7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6a7e 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=6a7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a7e OCA], [~~http~~://pdbe.org/6a7e PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6a7e RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6a7e PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6a7e ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] Defects in DHFR are the cause of megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:[~~http~~://omim.org/entry/613839 613839]]. DHFRD is an inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.<ref>PMID:21310276</ref> <ref>PMID:21310277</ref>	+	[https://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN] Defects in DHFR are the cause of megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:[https://omim.org/entry/613839 613839]. DHFRD is an inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.<ref>PMID:21310276</ref> <ref>PMID:21310277</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.<ref>PMID:21876188</ref> <ref>PMID:12096917</ref>	+	[https://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN] Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.<ref>PMID:21876188</ref> <ref>PMID:12096917</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6a7e" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6a7e" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Dihydrofolate reductase~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chitnumsub, P]]	+	[[Category: Chitnumsub P]]
-	[[Category: Kamchonwongpaisan, S]]	+	[[Category: Kamchonwongpaisan S]]
-	[[Category: Tarnchompoo, B]]	+	[[Category: Tarnchompoo B]]
-	[[Category: Vanichtanankul, J]]	+	[[Category: Vanichtanankul J]]
-	[[Category: Yuthavong, Y]]	+	[[Category: Yuthavong Y]]
-	~~[[Category: Antifolate]]~~	+
-	~~[[Category: Dhfr]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 07:06, 10 April 2019

OCA — Wed, 10 Apr 2019 07:06:52 GMT

←Older revision		Revision as of 07:06, 10 April 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6a7e is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Human dihydrofolate reductase complexed with NADPH and BT2==
		+	<StructureSection load='6a7e' size='340' side='right'caption='[[6a7e]], [[Resolution\|resolution]] 1.85Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6a7e]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A7E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6A7E FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9QR:5-(4-{3-[(2,4-diamino-6-ethylpyrimidin-5-yl)oxy]propoxy}phenyl)-6-ethylpyrimidine-2,4-diamine'>9QR</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6a7c\|6a7c]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </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=6a7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a7e OCA], [http://pdbe.org/6a7e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6a7e RCSB], [http://www.ebi.ac.uk/pdbsum/6a7e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6a7e ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] Defects in DHFR are the cause of megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:[http://omim.org/entry/613839 613839]]. DHFRD is an inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.<ref>PMID:21310276</ref> <ref>PMID:21310277</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/DYR_HUMAN DYR_HUMAN]] Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.<ref>PMID:21876188</ref> <ref>PMID:12096917</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The S108N mutation of dihydrofolate reductase (DHFR) renders Plasmodium falciparum malaria parasites resistant to pyrimethamine through steric clash with the rigid side chain of the inhibitor. Inhibitors with flexible side chains can avoid this clash and retain effectiveness against the mutant. However, other mutations such as N108S reversion confer resistance to flexible inhibitors. We designed and synthesized hybrid inhibitors with two structural types in a single molecule, which are effective against both wild-type and multiple mutants of P. falciparum through their selective target binding, as demonstrated by X-ray crystallography. Furthermore, the hybrid inhibitors can forestall the emergence of new resistant mutants, as shown by selection of mutants resistant to hybrid compound BT1 from a diverse PfDHFR random mutant library expressed in a surrogate bacterial system. These results show that it is possible to develop effective antifolate antimalarials to which the range of parasite resistance mutations is greatly reduced.

-	~~Authors: Vanichtanankul, J~~., Tarnchompoo, B., Chitnumsub, P., ~~Kamchonwongpaisan~~, S., ~~Yuthavong~~, Y.	+	Hybrid Inhibitors of Malarial Dihydrofolate Reductase with Dual Binding Modes That Can Forestall Resistance.,Tarnchompoo B, Chitnumsub P, Jaruwat A, Shaw PJ, Vanichtanankul J, Poen S, Rattanajak R, Wongsombat C, Tonsomboon A, Decharuangsilp S, Anukunwithaya T, Arwon U, Kamchonwongpaisan S, Yuthavong Y ACS Med Chem Lett. 2018 Nov 7;9(12):1235-1240. doi:, 10.1021/acsmedchemlett.8b00389. eCollection 2018 Dec 13. PMID:30613332<ref>PMID:30613332</ref>

-	~~Description~~: ~~Human dihydrofolate reductase complexed with NADPH and BT2~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Yuthavong, Y~~]]	+	<div class="pdbe-citations 6a7e" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Dihydrofolate reductase]]
		+	[[Category: Large Structures]]
	[[Category: Chitnumsub, P]]		[[Category: Chitnumsub, P]]
-	[[Category: Vanichtanankul, J]]
-	[[Category: Tarnchompoo, B]]
	[[Category: Kamchonwongpaisan, S]]		[[Category: Kamchonwongpaisan, S]]
		+	[[Category: Tarnchompoo, B]]
		+	[[Category: Vanichtanankul, J]]
		+	[[Category: Yuthavong, Y]]
		+	[[Category: Antifolate]]
		+	[[Category: Dhfr]]
		+	[[Category: Inhibitor]]
		+	[[Category: Oxidoreductase]]

OCA: Protected "6a7e" [edit=sysop:move=sysop]

OCA — Wed, 11 Jul 2018 03:57:02 GMT

Protected "6a7e" [edit=sysop:move=sysop]

←Older revision

Revision as of 03:57, 11 July 2018

OCA: New page: '''Unreleased structure''' The entry 6a7e is ON HOLD until Paper Publication Authors: Vanichtanankul, J., Tarnchompoo, B., Chitnumsub, P., Kamchonwongpaisan, S., Yuthavong, Y. Descript...

OCA — Wed, 11 Jul 2018 03:57:00 GMT

New page: '''Unreleased structure''' The entry 6a7e is ON HOLD until Paper Publication Authors: Vanichtanankul, J., Tarnchompoo, B., Chitnumsub, P., Kamchonwongpaisan, S., Yuthavong, Y. Descript...

New page

'''Unreleased structure'''

The entry 6a7e is ON HOLD until Paper Publication

Authors: Vanichtanankul, J., Tarnchompoo, B., Chitnumsub, P., Kamchonwongpaisan, S., Yuthavong, Y.

Description: Human dihydrofolate reductase complexed with NADPH and BT2
[[Category: Unreleased Structures]]
[[Category: Yuthavong, Y]]
[[Category: Chitnumsub, P]]
[[Category: Vanichtanankul, J]]
[[Category: Tarnchompoo, B]]
[[Category: Kamchonwongpaisan, S]]