6a2p - Revision history

OCA at 09:15, 22 November 2023

2023-11-22T09:15:36Z

←Older revision		Revision as of 09:15, 22 November 2023
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	<StructureSection load='6a2p' size='340' side='right'caption='[[6a2p]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='6a2p' size='340' side='right'caption='[[6a2p]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6a2p]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A2P OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6A2P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6a2p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6A2P FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9RR:5,5-[propane-1,3-diylbis(oxy-4,1-phenylene)]bis(6-ethylpyrimidine-2,4-diamine)'>9RR</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</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]] 2.6Å</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=6a2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a2p OCA], [~~http~~://pdbe.org/6a2p PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6a2p RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6a2p PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6a2p ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9RR:5,5-[propane-1,3-diylbis(oxy-4,1-phenylene)]bis(6-ethylpyrimidine-2,4-diamine)'>9RR</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</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=6a2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a2p OCA], [https://pdbe.org/6a2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6a2p RCSB], [https://www.ebi.ac.uk/pdbsum/6a2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6a2p ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/D9N170_PLAFA D9N170_PLAFA]] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism (By similarity).[PIRNR:PIRNR000389]	+	[https://www.uniprot.org/uniprot/D9N170_PLAFA D9N170_PLAFA] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism (By similarity).[PIRNR:PIRNR000389]
	<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 6a2p" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6a2p" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chitnumsub, P]]	+	[[Category: Plasmodium falciparum]]
-	[[Category: Jaruwat, A]]	+	[[Category: Chitnumsub P]]
-	[[Category: Tarnchampoo, B]]	+	[[Category: Jaruwat A]]
-	[[Category: Yuthavong, Y]]	+	[[Category: Tarnchampoo B]]
-	~~[[Category: Dual-binding inhibitor]]~~	+	[[Category: Yuthavong Y]]
-	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]~~	+
-	~~[[Category: Rossmann fold~~]]	+

OCA at 06:36, 24 April 2019

2019-04-24T06:36:09Z

←Older revision		Revision as of 06:36, 24 April 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6a2p is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of quadruple mutant (N51I+C59R+S108N+I164L) Plasmodium falciparum DHFR-TS complexed with BT3, NADPH, and dUMP==
		+	<StructureSection load='6a2p' size='340' side='right'caption='[[6a2p]], [[Resolution\|resolution]] 2.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6a2p]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A2P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6A2P FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9RR:5,5-[propane-1,3-diylbis(oxy-4,1-phenylene)]bis(6-ethylpyrimidine-2,4-diamine)'>9RR</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></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=6a2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a2p OCA], [http://pdbe.org/6a2p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6a2p RCSB], [http://www.ebi.ac.uk/pdbsum/6a2p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6a2p ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/D9N170_PLAFA D9N170_PLAFA]] Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism (By similarity).[PIRNR:PIRNR000389]
		+	<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: Chitnumsub~~, P., Jaruwat, A., ~~Tarnchampoo~~, B., ~~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: Crystal structure~~ of ~~quadruple mutant (N51I+C59R+S108N+I164L) Plasmodium falciparum DHFR-TS complexed with BT3, NADPH, and dUMP~~	+	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 6a2p" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Jaruwat, A~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Chitnumsub, P]]		[[Category: Chitnumsub, P]]
		+	[[Category: Jaruwat, A]]
	[[Category: Tarnchampoo, B]]		[[Category: Tarnchampoo, B]]
		+	[[Category: Yuthavong, Y]]
		+	[[Category: Dual-binding inhibitor]]
		+	[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
		+	[[Category: Rossmann fold]]

OCA at 07:05, 13 February 2019

2019-02-13T07:05:53Z

←Older revision		Revision as of 07:05, 13 February 2019
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6a2p is ON HOLD	+	The entry 6a2p is ON HOLD until Paper Publication

	Authors: Chitnumsub, P., Jaruwat, A., Tarnchampoo, B., Yuthavong, Y.		Authors: Chitnumsub, P., Jaruwat, A., Tarnchampoo, B., Yuthavong, Y.

OCA: Protected "6a2p" [edit=sysop:move=sysop]

2018-06-20T03:55:35Z

Protected "6a2p" [edit=sysop:move=sysop]

←Older revision

Revision as of 03:55, 20 June 2018

OCA: New page: '''Unreleased structure''' The entry 6a2p is ON HOLD Authors: Chitnumsub, P., Jaruwat, A., Tarnchampoo, B., Yuthavong, Y. Description: Crystal structure of quadruple mutant (N51I+C59R+...

2018-06-20T03:55:34Z

New page: '''Unreleased structure''' The entry 6a2p is ON HOLD Authors: Chitnumsub, P., Jaruwat, A., Tarnchampoo, B., Yuthavong, Y. Description: Crystal structure of quadruple mutant (N51I+C59R+...

New page

'''Unreleased structure'''

The entry 6a2p is ON HOLD

Authors: Chitnumsub, P., Jaruwat, A., Tarnchampoo, B., Yuthavong, Y.

Description: Crystal structure of quadruple mutant (N51I+C59R+S108N+I164L) Plasmodium falciparum DHFR-TS complexed with BT3, NADPH, and dUMP
[[Category: Unreleased Structures]]
[[Category: Yuthavong, Y]]
[[Category: Jaruwat, A]]
[[Category: Chitnumsub, P]]
[[Category: Tarnchampoo, B]]