OCA at 08:18, 11 October 2023

OCA — Wed, 11 Oct 2023 08:18:26 GMT

←Older revision		Revision as of 08:18, 11 October 2023
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	==Mycobacterium tuberculosis dihydrofolate reductase in complex with 3-(piperidin-1-ylmethyl)benzoic acid(fragment 11)==		==Mycobacterium tuberculosis dihydrofolate reductase in complex with 3-(piperidin-1-ylmethyl)benzoic acid(fragment 11)==
-	<StructureSection load='6vs9' size='340' side='right'caption='[[6vs9]]' scene=''>	+	<StructureSection load='6vs9' size='340' side='right'caption='[[6vs9]], [[Resolution\|resolution]] 1.84Å' 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=6VS9 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6VS9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6vs9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Ra Mycobacterium tuberculosis H37Ra]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VS9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VS9 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=6vs9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vs9 OCA], [~~http~~://pdbe.org/6vs9 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6vs9 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6vs9 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6vs9 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]] 1.842Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=RK4:3-[(piperidin-1-yl)methyl]benzoic+acid'>RK4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6vs9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vs9 OCA], [https://pdbe.org/6vs9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vs9 RCSB], [https://www.ebi.ac.uk/pdbsum/6vs9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vs9 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/A5U6B6_MYCTA A5U6B6_MYCTA] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.[PIRNR:PIRNR000194]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Dihydrofolate reductase (DHFR), a key enzyme involved in folate metabolism, is a widely explored target in the treatment of cancer, immune diseases, bacteria, and protozoa infections. Although several antifolates have proved successful in the treatment of infectious diseases, they have been underexplored to combat tuberculosis, despite the essentiality of M. tuberculosis DHFR (MtDHFR). Herein, we describe an integrated fragment-based drug discovery approach to target MtDHFR that has identified hits with scaffolds not yet explored in any previous drug design campaign for this enzyme. The application of a SAR by catalog strategy of an in house library for one of the identified fragments has led to a series of molecules that bind to MtDHFR with low micromolar affinities. Crystal structures of MtDHFR in complex with compounds of this series demonstrated a novel binding mode that considerably differs from other DHFR antifolates, thus opening perspectives for the development of relevant MtDHFR inhibitors.
		+
		+	Using a Fragment-Based Approach to Identify Alternative Chemical Scaffolds Targeting Dihydrofolate Reductase from Mycobacterium tuberculosis.,Ribeiro JA, Hammer A, Libreros-Zuniga GA, Chavez-Pacheco SM, Tyrakis P, de Oliveira GS, Kirkman T, El Bakali J, Rocco SA, Sforca ML, Parise-Filho R, Coyne AG, Blundell TL, Abell C, Dias MVB ACS Infect Dis. 2020 Aug 14;6(8):2192-2201. doi: 10.1021/acsinfecdis.0c00263., Epub 2020 Jul 10. PMID:32603583<ref>PMID:32603583</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6vs9" 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: Mycobacterium tuberculosis H37Ra]]
	[[Category: Dias MVB]]		[[Category: Dias MVB]]
	[[Category: Ribeiro JA]]		[[Category: Ribeiro JA]]

OCA at 11:35, 26 August 2020

OCA — Wed, 26 Aug 2020 11:35:09 GMT

←Older revision		Revision as of 11:35, 26 August 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6vs9 ~~is ON HOLD until Paper Publication~~	+	==Mycobacterium tuberculosis dihydrofolate reductase in complex with 3-(piperidin-1-ylmethyl)benzoic acid(fragment 11)==
-		+	<StructureSection load='6vs9' size='340' side='right'caption='[[6vs9]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VS9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VS9 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=6vs9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vs9 OCA], [http://pdbe.org/6vs9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vs9 RCSB], [http://www.ebi.ac.uk/pdbsum/6vs9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vs9 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Dias MVB]]
		+	[[Category: Ribeiro JA]]

OCA at 03:54, 13 May 2020

OCA — Wed, 13 May 2020 03:54:17 GMT

←Older revision		Revision as of 03:54, 13 May 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6vs9 is ON HOLD	+	The entry 6vs9 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6vs9" [edit=sysop:move=sysop]

OCA — Wed, 19 Feb 2020 05:20:11 GMT

Protected "6vs9" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:20, 19 February 2020

OCA: New page: '''Unreleased structure''' The entry 6vs9 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 19 Feb 2020 05:20:10 GMT

New page: '''Unreleased structure''' The entry 6vs9 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6vs9 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

6vs9 - Revision history

OCA at 08:18, 11 October 2023

OCA at 11:35, 26 August 2020

OCA at 03:54, 13 May 2020

OCA: Protected "6vs9" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6vs9 is ON HOLD Authors: Description: Category: Unreleased Structures