OCA at 08:18, 11 October 2023

2023-10-11T08:18:31Z

←Older revision		Revision as of 08:18, 11 October 2023
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	==Mycobacterium tuberculosis dihydrofolate reductase in complex with 3-(phenoxymethyl)benzoic acid(fragment 14)==		==Mycobacterium tuberculosis dihydrofolate reductase in complex with 3-(phenoxymethyl)benzoic acid(fragment 14)==
-	<StructureSection load='6vse' size='340' side='right'caption='[[6vse]]' scene=''>	+	<StructureSection load='6vse' size='340' side='right'caption='[[6vse]], [[Resolution\|resolution]] 1.76Å' 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=6VSE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6VSE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6vse]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VSE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VSE 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=6vse FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vse OCA], [~~http~~://pdbe.org/6vse PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6vse RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6vse PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6vse 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]] 1.758Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4RG:3-(PHENOXYMETHYL)BENZOIC+ACID'>4RG</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=6vse FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vse OCA], [https://pdbe.org/6vse PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vse RCSB], [https://www.ebi.ac.uk/pdbsum/6vse PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vse ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/DYR_MYCTU DYR_MYCTU] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
		+	<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 6vse" 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 H37Rv]]
	[[Category: Dias MVB]]		[[Category: Dias MVB]]
	[[Category: Ribeiro JA]]		[[Category: Ribeiro JA]]

OCA at 11:35, 26 August 2020

2020-08-26T11:35:14Z

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

-	~~The entry~~ 6vse ~~is ON HOLD until Paper Publication~~	+	==Mycobacterium tuberculosis dihydrofolate reductase in complex with 3-(phenoxymethyl)benzoic acid(fragment 14)==
-		+	<StructureSection load='6vse' size='340' side='right'caption='[[6vse]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VSE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VSE 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=6vse FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vse OCA], [http://pdbe.org/6vse PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vse RCSB], [http://www.ebi.ac.uk/pdbsum/6vse PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vse 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

2020-05-13T03:54:22Z

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

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

	Authors:		Authors:

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

2020-02-19T05:20:19Z

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

←Older revision

Revision as of 05:20, 19 February 2020

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

2020-02-19T05:20:18Z

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

New page

'''Unreleased structure'''

The entry 6vse is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

6vse - 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 "6vse" [edit=sysop:move=sysop]

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