OCA at 10:58, 22 November 2023

2023-11-22T10:58:44Z

← Older revision		Revision as of 10:58, 22 November 2023
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	==Quadruple mutant (N51I+C59R+S108N+I164L) plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with compound 46 and NADPH==		==Quadruple mutant (N51I+C59R+S108N+I164L) plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with compound 46 and NADPH==
	<StructureSection load='6lev' size='340' side='right'caption='[[6lev]]' scene=''>		<StructureSection load='6lev' size='340' side='right'caption='[[6lev]], [[Resolution\|resolution]] 2.64Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LEV OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6LEV FirstGlance]. <br>		<table><tr><td colspan='2'>[[6lev]] 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=6LEV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LEV FirstGlance]. <br>
	</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=6lev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lev OCA], [~~http~~://pdbe.org/6lev PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6lev RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6lev PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6lev ProSAT]</span></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]] 2.644Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EA0:2-[[4,6-bis(azanyl)-2,2-dimethyl-1,3,5-triazin-1-yl]oxy]-N-(4-chlorophenyl)ethanamide'>EA0</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=6lev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lev OCA], [https://pdbe.org/6lev PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lev RCSB], [https://www.ebi.ac.uk/pdbsum/6lev PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lev ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[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;">
			== Publication Abstract from PubMed ==
			A series of flexible diaminodihydrotriazines or cycloguanil (Cyc) analogues are developed and shown to inhibit P. falciparum dihydrofolate reductase (PfDHFR) of the wild type or those carrying either single (S108N), double (C59R + S108N and A16V + S108T), triple (N51I + C59R + S108N and C59R + S108N + I164L) or quadruple (N51I + C59R + S108N + I164L) mutations, responsible for antifolate resistance. The flexibility of the side chain at position N(1) has been included in the design so as to avoid unfavourable steric interaction with the side chain of residue 108 of the resistant mutants. The inhibition constants of many inhibitors for the mutant enzymes are in the low nanomolar region. Regaining of drug binding efficacies was achieved with both A16V and S108N series of mutants. X-ray studies of some enzyme-inhibitor complexes designed for optimal interaction with the mutant enzymes reveal the modes of binding in line with the Ki values. A number of these compounds show excellent antimalarial activities against resistant P. falciparum bearing the mutant enzymes, and exhibit low cytotoxicity to mammalian cells, making them good candidates for further development as antimalarial drugs.

			Flexible diaminodihydrotriazine inhibitors of Plasmodium falciparum dihydrofolate reductase: Binding strengths, modes of binding and their antimalarial activities.,Kamchonwongpaisan S, Charoensetakul N, Srisuwannaket C, Taweechai S, Rattanajak R, Vanichtanankul J, Vitsupakorn D, Arwon U, Thongpanchang C, Tarnchompoo B, Vilaivan T, Yuthavong Y Eur J Med Chem. 2020 Jun 1;195:112263. doi: 10.1016/j.ejmech.2020.112263. Epub, 2020 Mar 25. PMID:32294614<ref>PMID:32294614</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 6lev" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
			[[Category: Plasmodium falciparum]]
	[[Category: Vanichtanankul J]]		[[Category: Vanichtanankul J]]
	[[Category: Vitsupakorn D]]		[[Category: Vitsupakorn D]]

OCA at 07:42, 2 December 2020

2020-12-02T07:42:48Z

← Older revision		Revision as of 07:42, 2 December 2020
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	~~'''Unreleased structure'''~~

	~~The entry~~ 6lev is ~~ON HOLD until Paper Publication~~		==Quadruple mutant (N51I+C59R+S108N+I164L) plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) complexed with compound 46 and NADPH==
			<StructureSection load='6lev' size='340' side='right'caption='[[6lev]]' scene=''>
	~~Authors~~:		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LEV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6LEV FirstGlance]. <br>
	~~Description~~:		</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=6lev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lev OCA], [http://pdbe.org/6lev PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lev RCSB], [http://www.ebi.ac.uk/pdbsum/6lev PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lev ProSAT]</span></td></tr>
	[[Category: ~~Unreleased Structures~~]]		</table>
			__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: Vanichtanankul J]]
			[[Category: Vitsupakorn D]]

OCA at 05:26, 8 April 2020

2020-04-08T05:26:23Z

← Older revision		Revision as of 05:26, 8 April 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 6lev is ON HOLD		The entry 6lev is ON HOLD until Paper Publication

	Authors:		Authors:

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

2019-12-04T06:20:38Z

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

← Older revision	Revision as of 06:20, 4 December 2019
(No difference)

OCA: New page: '''Unreleased structure''' The entry 6lev is ON HOLD Authors: Description: Category: Unreleased Structures

2019-12-04T06:20:37Z

New page: '''Unreleased structure''' The entry 6lev is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6lev is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

6lev - Revision history

OCA at 10:58, 22 November 2023

OCA at 07:42, 2 December 2020

OCA at 05:26, 8 April 2020

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

OCA: New page: '''Unreleased structure''' The entry 6lev is ON HOLD Authors: Description: Category: Unreleased Structures