3qfx - Revision history

OCA at 08:35, 20 March 2024

OCA — Wed, 20 Mar 2024 08:35:06 GMT

←Older revision		Revision as of 08:35, 20 March 2024
Line 3:		Line 3:
	<StructureSection load='3qfx' size='340' side='right'caption='[[3qfx]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3qfx' size='340' side='right'caption='[[3qfx]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3qfx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Trybr Trybr~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QFX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3qfx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_rhodesiense Trypanosoma brucei rhodesiense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QFX FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=CP6:5~~-~~(4-CHLORO-PHENYL)-6-ETHYL-PYRIMIDINE-2~~,~~4-DIAMINE'>CP6</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]] 2.2Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>~~[[~~Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto~~; ~~max-height: 3em;'>[[3qg2\|3qg2]], [[3qgt\|3qgt]], [[3rg9\|3rg9]]</div>~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CP6:5-(4-CHLORO-PHENYL)-6-ETHYL-PYRIMIDINE-2,4-DIAMINE'>CP6</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>DHFR ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~31286 TRYBR])</td~~><~~/tr>~~	+
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks~~'>~~[https://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [https://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=3qfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qfx OCA], [https://pdbe.org/3qfx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qfx RCSB], [https://www.ebi.ac.uk/pdbsum/3qfx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qfx 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=3qfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qfx OCA], [https://pdbe.org/3qfx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qfx RCSB], [https://www.ebi.ac.uk/pdbsum/3qfx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qfx ProSAT]</span></td></tr>
	</table>		</table>
-	~~<div style="background-color:#fffaf0;">~~	+	== Function ==
-	== ~~Publication Abstract from PubMed~~ ==	+	[https://www.uniprot.org/uniprot/DRTS_TRYBB DRTS_TRYBB] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP (By similarity).
-	~~Dihydrofolate reductase (DHFR) is a potential drug target for Trypanosoma brucei, a human parasite, which is the causative agent for African sleeping sickness~~. ~~No drug is available against this target, since none of the classical antifolates such as pyrimethamine (PYR), cycloguanil, or trimethoprim are effective as selective inhibitors of T~~. brucei DHFR (TbDHFR). In order to design effective drugs that target TbDHFR, co-crystal structures with bound antifolates were studied. On comparison with malarial Plasmodium falciparum DHFR (PfDHFR), the co-crystal structures of wild-type TbDHFR reveal greater structural similarities to a mutant PfDHFR causing antifolate resistance than the wild-type enzyme. TbDHFR imposes steric hindrance for rigid inhibitors like PYR around Thr86, which is equivalent to Ser108Asn of the malarial enzymes. In addition, a missing residue on TbDHFR active-site loop together with the presence of Ile51 widens its active site even further than the structural effect of Asn51Ile, which is observed in ~~PfDHFR structures~~. ~~The structural similarities are paralleled by the similarly poor affinities of the trypanosomal~~ enzyme ~~for rigid inhibitors~~. ~~Mutations of TbDHFR at Thr86 resulted in 10-fold enhancement or 7-fold reduction in the rigid inhibitors affinities~~ for ~~Thr86Ser or Thr86Asn~~, respectively. The co-crystal structure of TbDHFR with a flexible antifolate WR99210 suggests that its greater affinity result from its ability to avoid such Thr86 clash and occupy the widened binding space similarly to what is observed in the PfDHFR structures. Natural resistance to antifolates of TbDHFR can therefore be explained, and ~~potential antifolate chemotherapy of trypanosomiasis should be possible taking this into account.~~	+
-		+
-	Trypanosomal Dihydrofolate Reductase Reveals Natural Antifolate Resistance.,Vanichtanankul J, Taweechai S, Yuvaniyama J, Vilaivan T, Chitnumsub P, Kamchonwongpaisan S, Yuthavong Y ACS Chem Biol. 2011 Jun 16. PMID:21650210<ref>PMID:21650210</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of~~ the ~~U.S. National Library~~ of ~~Medicine~~.~~<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3qfx" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]		*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Dihydrofolate reductase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Trybr~~]]	+	[[Category: Trypanosoma brucei rhodesiense]]
-	[[Category: Chitnumsub, P]]	+	[[Category: Chitnumsub P]]
-	[[Category: Kamchonwongpaisan, S]]	+	[[Category: Kamchonwongpaisan S]]
-	[[Category: Taweechai, S]]	+	[[Category: Taweechai S]]
-	[[Category: Vanichtanankul, J]]	+	[[Category: Vanichtanankul J]]
-	[[Category: Yuthavong, Y]]	+	[[Category: Yuthavong Y]]
-	[[Category: Yuvaniyama, J]]	+	[[Category: Yuvaniyama J]]
-	~~[[Category: Antifolate resistance]]~~	+
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]~~	+
-	~~[[Category: Pyrimethamine]]~~	+
-	~~[[Category: Trypanosome~~]]	+

OCA at 06:07, 8 June 2022

OCA — Wed, 08 Jun 2022 06:07:25 GMT

←Older revision		Revision as of 06:07, 8 June 2022
Line 1:		Line 1:

	==Trypanosoma brucei dihydrofolate reductase pyrimethamine complex==		==Trypanosoma brucei dihydrofolate reductase pyrimethamine complex==
-	<StructureSection load='3qfx' size='340' side='right' caption='[[3qfx]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='3qfx' size='340' side='right'caption='[[3qfx]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3qfx]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Trybr Trybr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3QFX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3qfx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trybr Trybr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QFX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CP6:5-(4-CHLORO-PHENYL)-6-ETHYL-PYRIMIDINE-2,4-DIAMINE'>CP6</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CP6:5-(4-CHLORO-PHENYL)-6-ETHYL-PYRIMIDINE-2,4-DIAMINE'>CP6</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">[[3qg2\|3qg2]], [[3qgt\|3qgt]], [[3rg9\|3rg9]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qg2\|3qg2]], [[3qgt\|3qgt]], [[3rg9\|3rg9]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHFR ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31286 TRYBR])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHFR ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31286 TRYBR])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [https://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=3qfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qfx OCA], [~~http~~://pdbe.org/3qfx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3qfx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3qfx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3qfx 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=3qfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qfx OCA], [https://pdbe.org/3qfx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qfx RCSB], [https://www.ebi.ac.uk/pdbsum/3qfx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qfx ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	==See Also==		==See Also==
-	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]	+	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
		+	[[Category: Large Structures]]
	[[Category: Trybr]]		[[Category: Trybr]]
	[[Category: Chitnumsub, P]]		[[Category: Chitnumsub, P]]

OCA at 10:07, 4 August 2016

OCA — Thu, 04 Aug 2016 10:07:15 GMT

←Older revision		Revision as of 10:07, 4 August 2016
Line 1:		Line 1:
		+
	==Trypanosoma brucei dihydrofolate reductase pyrimethamine complex==		==Trypanosoma brucei dihydrofolate reductase pyrimethamine complex==
	<StructureSection load='3qfx' size='340' side='right' caption='[[3qfx]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3qfx' size='340' side='right' caption='[[3qfx]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3qfx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Trypanosoma_brucei_rhodesiense Trypanosoma brucei rhodesiense~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QFX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3qfx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trybr Trybr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QFX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CP6:5-(4-CHLORO-PHENYL)-6-ETHYL-PYRIMIDINE-2,4-DIAMINE'>CP6</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CP6:5-(4-CHLORO-PHENYL)-6-ETHYL-PYRIMIDINE-2,4-DIAMINE'>CP6</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">[[3qg2\|3qg2]], [[3qgt\|3qgt]], [[3rg9\|3rg9]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3qg2\|3qg2]], [[3qgt\|3qgt]], [[3rg9\|3rg9]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHFR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31286 ~~Trypanosoma brucei rhodesiense~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHFR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31286 TRYBR])</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='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=3qfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qfx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qfx RCSB], [http://www.ebi.ac.uk/pdbsum/3qfx 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=3qfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qfx OCA], [http://pdbe.org/3qfx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qfx RCSB], [http://www.ebi.ac.uk/pdbsum/3qfx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qfx ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 17:		Line 18:
	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 3qfx" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
-	[[Category: ~~Trypanosoma brucei rhodesiense~~]]	+	[[Category: Trybr]]
	[[Category: Chitnumsub, P]]		[[Category: Chitnumsub, P]]
	[[Category: Kamchonwongpaisan, S]]		[[Category: Kamchonwongpaisan, S]]

OCA at 10:31, 19 December 2014

OCA — Fri, 19 Dec 2014 10:31:21 GMT

←Older revision		Revision as of 10:31, 19 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3qfx~~\| ~~PDB~~=3qfx \| ~~SCENE~~= }}	+	==Trypanosoma brucei dihydrofolate reductase pyrimethamine complex==
-	===Trypanosoma brucei ~~dihydrofolate~~ reductase ~~pyrimethamine complex~~===	+	<StructureSection load='3qfx' size='340' side='right' caption='[[3qfx]], [[Resolution\|resolution]] 2.20Å' scene=''>
-	~~{{ABSTRACT_PUBMED_21650210}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3qfx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_brucei_rhodesiense Trypanosoma brucei rhodesiense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QFX FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CP6:5-(4-CHLORO-PHENYL)-6-ETHYL-PYRIMIDINE-2,4-DIAMINE'>CP6</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">[[3qg2\|3qg2]], [[3qgt\|3qgt]], [[3rg9\|3rg9]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DHFR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31286 Trypanosoma brucei rhodesiense])</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=3qfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qfx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qfx RCSB], [http://www.ebi.ac.uk/pdbsum/3qfx PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Dihydrofolate reductase (DHFR) is a potential drug target for Trypanosoma brucei, a human parasite, which is the causative agent for African sleeping sickness. No drug is available against this target, since none of the classical antifolates such as pyrimethamine (PYR), cycloguanil, or trimethoprim are effective as selective inhibitors of T. brucei DHFR (TbDHFR). In order to design effective drugs that target TbDHFR, co-crystal structures with bound antifolates were studied. On comparison with malarial Plasmodium falciparum DHFR (PfDHFR), the co-crystal structures of wild-type TbDHFR reveal greater structural similarities to a mutant PfDHFR causing antifolate resistance than the wild-type enzyme. TbDHFR imposes steric hindrance for rigid inhibitors like PYR around Thr86, which is equivalent to Ser108Asn of the malarial enzymes. In addition, a missing residue on TbDHFR active-site loop together with the presence of Ile51 widens its active site even further than the structural effect of Asn51Ile, which is observed in PfDHFR structures. The structural similarities are paralleled by the similarly poor affinities of the trypanosomal enzyme for rigid inhibitors. Mutations of TbDHFR at Thr86 resulted in 10-fold enhancement or 7-fold reduction in the rigid inhibitors affinities for Thr86Ser or Thr86Asn, respectively. The co-crystal structure of TbDHFR with a flexible antifolate WR99210 suggests that its greater affinity result from its ability to avoid such Thr86 clash and occupy the widened binding space similarly to what is observed in the PfDHFR structures. Natural resistance to antifolates of TbDHFR can therefore be explained, and potential antifolate chemotherapy of trypanosomiasis should be possible taking this into account.

-	~~==About this Structure==~~	+	Trypanosomal Dihydrofolate Reductase Reveals Natural Antifolate Resistance.,Vanichtanankul J, Taweechai S, Yuvaniyama J, Vilaivan T, Chitnumsub P, Kamchonwongpaisan S, Yuthavong Y ACS Chem Biol. 2011 Jun 16. PMID:21650210<ref>PMID:21650210</ref>
-	~~[[3qfx]] is a 2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Trypanosoma_brucei_rhodesiense Trypanosoma brucei rhodesiense]~~. ~~Full crystallographic information is available from [http~~:/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3QFX OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group~~=~~"xtra">PMID:021650210</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+
		+	==See Also==
		+	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Trypanosoma brucei rhodesiense]]		[[Category: Trypanosoma brucei rhodesiense]]
-	[[Category: Chitnumsub, P.]]	+	[[Category: Chitnumsub, P]]
-	[[Category: Kamchonwongpaisan, S.]]	+	[[Category: Kamchonwongpaisan, S]]
-	[[Category: Taweechai, S.]]	+	[[Category: Taweechai, S]]
-	[[Category: Vanichtanankul, J.]]	+	[[Category: Vanichtanankul, J]]
-	[[Category: Yuthavong, Y.]]	+	[[Category: Yuthavong, Y]]
-	[[Category: Yuvaniyama, J.]]	+	[[Category: Yuvaniyama, J]]
	[[Category: Antifolate resistance]]		[[Category: Antifolate resistance]]
-	[[Category: Dihydrofolate reductase]]
	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]		[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
	[[Category: Pyrimethamine]]		[[Category: Pyrimethamine]]
	[[Category: Trypanosome]]		[[Category: Trypanosome]]

OCA at 07:57, 30 June 2013

OCA — Sun, 30 Jun 2013 07:57:35 GMT

←Older revision		Revision as of 07:57, 30 June 2013
Line 1:		Line 1:
-	[[Image:3qfx.png\|left\|200px]]
-
	{{STRUCTURE_3qfx\| PDB=3qfx \| SCENE= }}		{{STRUCTURE_3qfx\| PDB=3qfx \| SCENE= }}
-
	===Trypanosoma brucei dihydrofolate reductase pyrimethamine complex===		===Trypanosoma brucei dihydrofolate reductase pyrimethamine complex===
-
	{{ABSTRACT_PUBMED_21650210}}		{{ABSTRACT_PUBMED_21650210}}

	==About this Structure==		==About this Structure==
	[[3qfx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_brucei_rhodesiense Trypanosoma brucei rhodesiense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFX OCA].		[[3qfx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_brucei_rhodesiense Trypanosoma brucei rhodesiense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFX OCA].
-
-	==See Also==
-	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:021650210</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021650210</ref><references group="xtra"/><references/>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Trypanosoma brucei rhodesiense]]		[[Category: Trypanosoma brucei rhodesiense]]

OCA at 14:30, 20 October 2012

OCA — Sat, 20 Oct 2012 14:30:48 GMT

←Older revision		Revision as of 14:30, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3qfx]] is a 2 chain structure ~~of [[Dihydrofolate reductase]]~~ with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_brucei_rhodesiense Trypanosoma brucei rhodesiense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFX OCA].	+	[[3qfx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_brucei_rhodesiense Trypanosoma brucei rhodesiense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFX OCA].

	==See Also==		==See Also==

OCA at 15:22, 26 July 2012

OCA — Thu, 26 Jul 2012 15:22:46 GMT

←Older revision		Revision as of 15:22, 26 July 2012
Line 1:		Line 1:
-	[[Image:3qfx.~~jpg~~\|left\|200px]]	+	[[Image:3qfx.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3qfx", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3qfx\| PDB=3qfx \| SCENE= }}		{{STRUCTURE_3qfx\| PDB=3qfx \| SCENE= }}

	===Trypanosoma brucei dihydrofolate reductase pyrimethamine complex===		===Trypanosoma brucei dihydrofolate reductase pyrimethamine complex===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_21650210}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 21650210 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_21650210}}		{{ABSTRACT_PUBMED_21650210}}

	==About this Structure==		==About this Structure==
-	[[3qfx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_brucei_rhodesiense Trypanosoma brucei rhodesiense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFX OCA].	+	[[3qfx]] is a 2 chain structure of [[Dihydrofolate reductase]] with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_brucei_rhodesiense Trypanosoma brucei rhodesiense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFX OCA].
		+
		+	==See Also==
		+	*[[Dihydrofolate reductase\|Dihydrofolate reductase]]

	==Reference==		==Reference==

OCA at 06:06, 29 June 2011

OCA — Wed, 29 Jun 2011 06:06:42 GMT

←Older revision		Revision as of 06:06, 29 June 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3qfx.jpg\|left\|200px]]

-	The ~~entry 3qfx~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3qfx", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3qfx\| PDB=3qfx \| SCENE= }}

-	~~Authors: Vanichtanankul, J., Yuvaniyama, J., Taweechai, S., Chitnumsub, P., Kamchonwongpaisan, S., Yuthavong, Y.~~	+	===Trypanosoma brucei dihydrofolate reductase pyrimethamine complex===

-	~~Description~~: Trypanosoma brucei ~~dihydrofolate~~ reductase ~~pyrimethamine~~ complex	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21650210}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21650210 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21650210}}
		+
		+	==About this Structure==
		+	[[3qfx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_brucei_rhodesiense Trypanosoma brucei rhodesiense]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QFX OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021650210</ref><references group="xtra"/>
		+	[[Category: Dihydrofolate reductase]]
		+	[[Category: Trypanosoma brucei rhodesiense]]
		+	[[Category: Chitnumsub, P.]]
		+	[[Category: Kamchonwongpaisan, S.]]
		+	[[Category: Taweechai, S.]]
		+	[[Category: Vanichtanankul, J.]]
		+	[[Category: Yuthavong, Y.]]
		+	[[Category: Yuvaniyama, J.]]
		+	[[Category: Antifolate resistance]]
		+	[[Category: Dihydrofolate reductase]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
		+	[[Category: Pyrimethamine]]
		+	[[Category: Trypanosome]]

OCA at 05:20, 16 February 2011

OCA — Wed, 16 Feb 2011 05:20:59 GMT

←Older revision		Revision as of 05:20, 16 February 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3qfx is ON HOLD	+	The entry 3qfx is ON HOLD until Paper Publication

	Authors: Vanichtanankul, J., Yuvaniyama, J., Taweechai, S., Chitnumsub, P., Kamchonwongpaisan, S., Yuthavong, Y.		Authors: Vanichtanankul, J., Yuvaniyama, J., Taweechai, S., Chitnumsub, P., Kamchonwongpaisan, S., Yuthavong, Y.

	Description: Trypanosoma brucei dihydrofolate reductase pyrimethamine complex		Description: Trypanosoma brucei dihydrofolate reductase pyrimethamine complex

OCA at 05:49, 9 February 2011

OCA — Wed, 09 Feb 2011 05:49:25 GMT

←Older revision		Revision as of 05:49, 9 February 2011
Line 3:		Line 3:
	The entry 3qfx is ON HOLD		The entry 3qfx is ON HOLD

-	Authors: Vanichtanankul, J, Yuvaniyama, J, Taweechai, S, Chitnumsub, P, Kamchonwongpaisan, S, Yuthavong, Y	+	Authors: Vanichtanankul, J., Yuvaniyama, J., Taweechai, S., Chitnumsub, P., Kamchonwongpaisan, S., Yuthavong, Y.

	Description: Trypanosoma brucei dihydrofolate reductase pyrimethamine complex		Description: Trypanosoma brucei dihydrofolate reductase pyrimethamine complex