6dds - Revision history

OCA at 06:03, 11 October 2023

2023-10-11T06:03:59Z

← Older revision		Revision as of 06:03, 11 October 2023
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	<StructureSection load='6dds' size='340' side='right'caption='[[6dds]], [[Resolution\|resolution]] 1.72Å' scene=''>		<StructureSection load='6dds' size='340' side='right'caption='[[6dds]], [[Resolution\|resolution]] 1.72Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6dds]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Myctu Myctu~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DDS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6DDS FirstGlance]. <br>		<table><tr><td colspan='2'>[[6dds]] is a 4 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=6DDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DDS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=U75:4-[3-[3-[2,4-BIS(AZANYL)-6-ETHYL-PYRIMIDIN-5-YL]PROP-2-YNYL]-5-METHOXY-PHENYL]BENZOIC+ACID'>U75</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]] 1.72Å</td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6ddp\|6ddp]]</td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=U75:4-[3-[3-[2,4-BIS(AZANYL)-6-ETHYL-PYRIMIDIN-5-YL]PROP-2-YNYL]-5-METHOXY-PHENYL]BENZOIC+ACID'>U75</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">folA, dfrA, Rv2763c, MTV002.28c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=6dds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dds OCA], [https://pdbe.org/6dds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dds RCSB], [https://www.ebi.ac.uk/pdbsum/6dds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dds ProSAT]</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=6dds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dds OCA], [~~http~~://pdbe.org/6dds PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6dds RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6dds PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6dds ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://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.		[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: Dihydrofolate reductase]]~~
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: ~~Myctu~~]]		[[Category: Mycobacterium tuberculosis H37Rv]]
	[[Category: Hajian, B]]		[[Category: Hajian B]]
	[[Category: Scocchera, E]]		[[Category: Scocchera E]]
	[[Category: Wright, D]]		[[Category: Wright D]]
	~~[[Category: Antifolate]]~~
	~~[[Category: Dhfr]]~~
	~~[[Category: Oxidoreductase-oxidoreductase inhibitor complex~~]]

OCA at 06:17, 10 July 2019

2019-07-10T06:17:23Z

← Older revision		Revision as of 06:17, 10 July 2019
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	==Mycobacterium tuberculosis Dihydrofolate Reductase complexed with beta-NADPH and 4-[3-[3-[2,4-bis(azanyl)-6-ethyl-pyrimidin-5-yl]prop-2-ynyl]-5-methoxy-phenyl]benzoic acid==		==Mycobacterium tuberculosis Dihydrofolate Reductase complexed with beta-NADPH and 4-[3-[3-[2,4-bis(azanyl)-6-ethyl-pyrimidin-5-yl]prop-2-ynyl]-5-methoxy-phenyl]benzoic acid==
	<StructureSection load='6dds' size='340' side='right' caption='[[6dds]], [[Resolution\|resolution]] 1.72Å' scene=''>		<StructureSection load='6dds' size='340' side='right'caption='[[6dds]], [[Resolution\|resolution]] 1.72Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6dds]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DDS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DDS FirstGlance]. <br>		<table><tr><td colspan='2'>[[6dds]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DDS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DDS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=U75:4-[3-[3-[2,4-BIS(AZANYL)-6-ETHYL-PYRIMIDIN-5-YL]PROP-2-YNYL]-5-METHOXY-PHENYL]BENZOIC+ACID'>U75</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=U75:4-[3-[3-[2,4-BIS(AZANYL)-6-ETHYL-PYRIMIDIN-5-YL]PROP-2-YNYL]-5-METHOXY-PHENYL]BENZOIC+ACID'>U75</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6ddp\|6ddp]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6ddp\|6ddp]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">folA, dfrA, Rv2763c, MTV002.28c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=6dds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dds OCA], [http://pdbe.org/6dds PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dds RCSB], [http://www.ebi.ac.uk/pdbsum/6dds PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dds ProSAT]</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=6dds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dds OCA], [http://pdbe.org/6dds PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dds RCSB], [http://www.ebi.ac.uk/pdbsum/6dds PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dds ProSAT]</span></td></tr>
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	== Function ==		== Function ==
	[[http://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.		[[http://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 ==
			The folate biosynthetic pathway offers many druggable targets that have yet to be exploited in tuberculosis therapy. Herein, we have identified a series of small molecules that interrupt Mycobacterium tuberculosis (Mtb) folate metabolism by dual targeting of dihydrofolate reductase (DHFR), a key enzyme in the folate pathway, and its functional analog, Rv2671. We have also compared the antifolate activity of these compounds with that of para-aminosalicylic acid (PAS). We found that the bioactive metabolite of PAS, in addition to previously reported activity against DHFR, inhibits flavin-dependent thymidylate synthase in Mtb, suggesting a multi-targeted mechanism of action for this drug. Finally, we have shown that antifolate treatment in Mtb decreases the production of mycolic acids, most likely due to perturbation of the activated methyl cycle. We conclude that multi-targeting of the folate pathway in Mtb is associated with highly potent anti-mycobacterial activity.

			Drugging the Folate Pathway in Mycobacterium tuberculosis: The Role of Multi-targeting Agents.,Hajian B, Scocchera E, Shoen C, Krucinska J, Viswanathan K, G-Dayanandan N, Erlandsen H, Estrada A, Mikusova K, Kordulakova J, Cynamon M, Wright D Cell Chem Biol. 2019 Jun 20;26(6):781-791.e6. doi:, 10.1016/j.chembiol.2019.02.013. Epub 2019 Mar 28. PMID:30930162<ref>PMID:30930162</ref>

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

			==See Also==
			*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
			[[Category: Large Structures]]
			[[Category: Myctu]]
	[[Category: Hajian, B]]		[[Category: Hajian, B]]
	[[Category: Scocchera, E]]		[[Category: Scocchera, E]]

OCA at 07:27, 23 May 2018

2018-05-23T07:27:40Z

← Older revision		Revision as of 07:27, 23 May 2018
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	~~'''Unreleased structure'''~~

	~~The entry 6dds is ON HOLD~~		==Mycobacterium tuberculosis Dihydrofolate Reductase complexed with beta-NADPH and 4-[3-[3-[2,4-bis(azanyl)-6-ethyl-pyrimidin-5-yl]prop-2-ynyl]-5-methoxy-phenyl]benzoic acid==
			<StructureSection load='6dds' size='340' side='right' caption='[[6dds]], [[Resolution\|resolution]] 1.72Å' scene=''>
	~~Authors: Hajian, B., Wright, D., Scocchera, E.~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[6dds]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DDS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DDS FirstGlance]. <br>
	~~Description:~~ Mycobacterium tuberculosis Dihydrofolate Reductase complexed with beta-NADPH and 3'-[3-(2,4-~~diamino~~-6-~~ethylphenyl)~~prop-2-yn-1-yl]-5'-~~methoxy~~-[1,1'-~~biphenyl~~]-4-~~carboxylic acid~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=U75:4-[3-[3-[2,4-BIS(AZANYL)-6-ETHYL-PYRIMIDIN-5-YL]PROP-2-YNYL]-5-METHOXY-PHENYL]BENZOIC+ACID'>U75</scene></td></tr>
	[[Category: ~~Unreleased Structures~~]]		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6ddp\|6ddp]]</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=6dds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dds OCA], [http://pdbe.org/6dds PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dds RCSB], [http://www.ebi.ac.uk/pdbsum/6dds PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dds ProSAT]</span></td></tr>
			</table>
			== Function ==
			[[http://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.
			__TOC__
			</StructureSection>
			[[Category: Dihydrofolate reductase]]
			[[Category: Hajian, B]]
	[[Category: Scocchera, E]]		[[Category: Scocchera, E]]
	[[Category: Wright, D]]		[[Category: Wright, D]]
	[[Category: ~~Hajian, B~~]]		[[Category: Antifolate]]
			[[Category: Dhfr]]
			[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

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

2018-05-16T04:10:19Z

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

← Older revision	Revision as of 04:10, 16 May 2018
(No difference)

OCA: New page: '''Unreleased structure''' The entry 6dds is ON HOLD Authors: Hajian, B., Wright, D., Scocchera, E. Description: Mycobacterium tuberculosis Dihydrofolate Reductase complexed with beta-...

2018-05-16T04:10:18Z

New page: '''Unreleased structure''' The entry 6dds is ON HOLD Authors: Hajian, B., Wright, D., Scocchera, E. Description: Mycobacterium tuberculosis Dihydrofolate Reductase complexed with beta-...

New page

'''Unreleased structure'''

The entry 6dds is ON HOLD

Authors: Hajian, B., Wright, D., Scocchera, E.

Description: Mycobacterium tuberculosis Dihydrofolate Reductase complexed with beta-NADPH and 3'-[3-(2,4-diamino-6-ethylphenyl)prop-2-yn-1-yl]-5'-methoxy-[1,1'-biphenyl]-4-carboxylic acid
[[Category: Unreleased Structures]]
[[Category: Scocchera, E]]
[[Category: Wright, D]]
[[Category: Hajian, B]]