6nne - Revision history

OCA at 14:48, 13 March 2024

OCA — Wed, 13 Mar 2024 14:48:36 GMT

←Older revision		Revision as of 14:48, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='6nne' size='340' side='right'caption='[[6nne]], [[Resolution\|resolution]] 1.59Å' scene=''>		<StructureSection load='6nne' size='340' side='right'caption='[[6nne]], [[Resolution\|resolution]] 1.59Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nne]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Mycta Mycta~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NNE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6NNE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nne]] 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=6NNE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NNE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=KUP:5-[(3,4-dimethoxyphenyl)methyl]pyrimidine-2,4-diamine'>KUP</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.595Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">dfrA, MRA_2788 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=419947 MYCTA])</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=KUP:5-[(3,4-dimethoxyphenyl)methyl]pyrimidine-2,4-diamine'>KUP</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=6nne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nne OCA], [https://pdbe.org/6nne PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nne RCSB], [https://www.ebi.ac.uk/pdbsum/6nne PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nne 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=6nne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nne OCA], [~~http~~://pdbe.org/6nne PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6nne RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6nne PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6nne ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://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]	+	[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 ==~~	+
-	Tuberculosis is a disease caused by Mycobacterium tuberculosis and is the leading cause of death from a single infectious pathogen, with a high prevalence in developing countries in Africa and Asia. There still is a need for the development or repurposing of novel therapies to combat this disease owing to the long-term nature of current therapies and because of the number of reported resistant strains. Here, structures of dihydrofolate reductase from M. tuberculosis (MtDHFR), which is a key target of the folate pathway, are reported in complex with four antifolates, pyrimethamine, cycloguanil, diaverdine and pemetrexed, and its substrate dihydrofolate in order to understand their binding modes. The structures of all of these complexes were obtained in the closed-conformation state of the enzyme and a fine structural analysis indicated motion in key regions of the substrate-binding site and different binding modes of the ligands. In addition, the affinities, through Kd measurement, of diaverdine and methotrexate have been determined; MtDHFR has a lower affinity (highest Kd) for diaverdine than pyrimethamine and trimethoprim, and a very high affinity for methotrexate, as expected. The structural comparisons and analysis described in this work provide new information about the plasticity of MtDHFR and the binding effects of different antifolates.	+

-	Crystal structures of the closed form of Mycobacterium tuberculosis dihydrofolate reductase in complex with dihydrofolate and antifolates.,Ribeiro JA, Chavez-Pacheco SM, de Oliveira GS, Silva CDS, Giudice JHP, Libreros-Zuniga GA, Dias MVB Acta Crystallogr D Struct Biol. 2019 Jul 1;75(Pt 7):682-693. doi:, 10.1107/S205979831900901X. Epub 2019 Jul 4. PMID:31282477<ref>PMID:31282477</ref>	+	==See Also==
-		+	*[[Dihydrofolate reductase 3D structures\|Dihydrofolate reductase 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 6nne" style~~=~~"background-color:#fffaf0;"></div>~~	+
-	~~== References~~ ==	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Dihydrofolate reductase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Mycta~~]]	+	[[Category: Mycobacterium tuberculosis H37Ra]]
-	[[Category: Chavez-Pacheco~~, S M~~]]	+	[[Category: Chavez-Pacheco SM]]
-	[[Category: Dias~~, M V.B~~]]	+	[[Category: Dias MVB]]
-	[[Category: Ribeiro~~, J A]]~~	+	[[Category: Ribeiro JA]]
-	~~[[Category: Antifolate]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 11:43, 13 November 2019

OCA — Wed, 13 Nov 2019 11:43:11 GMT

←Older revision		Revision as of 11:43, 13 November 2019
Line 3:		Line 3:
	<StructureSection load='6nne' size='340' side='right'caption='[[6nne]], [[Resolution\|resolution]] 1.59Å' scene=''>		<StructureSection load='6nne' size='340' side='right'caption='[[6nne]], [[Resolution\|resolution]] 1.59Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nne]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NNE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NNE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nne]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycta Mycta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NNE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NNE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=KUP:5-[(3,4-dimethoxyphenyl)methyl]pyrimidine-2,4-diamine'>KUP</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=KUP:5-[(3,4-dimethoxyphenyl)methyl]pyrimidine-2,4-diamine'>KUP</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">dfrA, MRA_2788 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=419947 MYCTA])</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=6nne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nne OCA], [http://pdbe.org/6nne PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nne RCSB], [http://www.ebi.ac.uk/pdbsum/6nne PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nne 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=6nne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nne OCA], [http://pdbe.org/6nne PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nne RCSB], [http://www.ebi.ac.uk/pdbsum/6nne PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nne ProSAT]</span></td></tr>
Line 10:		Line 11:
	== Function ==		== Function ==
	[[http://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]		[[http://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 ==
		+	Tuberculosis is a disease caused by Mycobacterium tuberculosis and is the leading cause of death from a single infectious pathogen, with a high prevalence in developing countries in Africa and Asia. There still is a need for the development or repurposing of novel therapies to combat this disease owing to the long-term nature of current therapies and because of the number of reported resistant strains. Here, structures of dihydrofolate reductase from M. tuberculosis (MtDHFR), which is a key target of the folate pathway, are reported in complex with four antifolates, pyrimethamine, cycloguanil, diaverdine and pemetrexed, and its substrate dihydrofolate in order to understand their binding modes. The structures of all of these complexes were obtained in the closed-conformation state of the enzyme and a fine structural analysis indicated motion in key regions of the substrate-binding site and different binding modes of the ligands. In addition, the affinities, through Kd measurement, of diaverdine and methotrexate have been determined; MtDHFR has a lower affinity (highest Kd) for diaverdine than pyrimethamine and trimethoprim, and a very high affinity for methotrexate, as expected. The structural comparisons and analysis described in this work provide new information about the plasticity of MtDHFR and the binding effects of different antifolates.
		+
		+	Crystal structures of the closed form of Mycobacterium tuberculosis dihydrofolate reductase in complex with dihydrofolate and antifolates.,Ribeiro JA, Chavez-Pacheco SM, de Oliveira GS, Silva CDS, Giudice JHP, Libreros-Zuniga GA, Dias MVB Acta Crystallogr D Struct Biol. 2019 Jul 1;75(Pt 7):682-693. doi:, 10.1107/S205979831900901X. Epub 2019 Jul 4. PMID:31282477<ref>PMID:31282477</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6nne" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Dihydrofolate reductase]]		[[Category: Dihydrofolate reductase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
		+	[[Category: Mycta]]
	[[Category: Chavez-Pacheco, S M]]		[[Category: Chavez-Pacheco, S M]]
	[[Category: Dias, M V.B]]		[[Category: Dias, M V.B]]

OCA at 10:46, 17 July 2019

OCA — Wed, 17 Jul 2019 10:46:23 GMT

←Older revision		Revision as of 10:46, 17 July 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6nne is ~~ON HOLD~~	+	==Crystal structure of Dihydrofolate reductase from Mycobacterium tuberculosis in complex with diaverdine==
-		+	<StructureSection load='6nne' size='340' side='right'caption='[[6nne]], [[Resolution\|resolution]] 1.59Å' scene=''>
-	~~Authors~~: ~~Ribeiro~~, J.A., ~~Chavez~~-~~Pacheco~~, S.M., ~~Dias~~, M.V.B.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6nne]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NNE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NNE FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure of~~ Dihydrofolate reductase ~~from Mycobacterium tuberculosis in complex with diaverdine~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=KUP:5-[(3,4-dimethoxyphenyl)methyl]pyrimidine-2,4-diamine'>KUP</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<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>
-	[[Category: ~~Ribeiro~~, ~~J.A~~]]	+	<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=6nne FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nne OCA], [http://pdbe.org/6nne PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nne RCSB], [http://www.ebi.ac.uk/pdbsum/6nne PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nne ProSAT]</span></td></tr>
-	[[Category: Dias, M.V.B]]	+	</table>
-	[[Category: ~~Chavez-Pacheco~~, ~~S.M~~]]	+	== Function ==
		+	[[http://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]
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Dihydrofolate reductase]]
		+	[[Category: Large Structures]]
		+	[[Category: Chavez-Pacheco, S M]]
		+	[[Category: Dias, M V.B]]
		+	[[Category: Ribeiro, J A]]
		+	[[Category: Antifolate]]
		+	[[Category: Oxidoreductase]]

OCA at 04:10, 19 June 2019

OCA — Wed, 19 Jun 2019 04:10:34 GMT

←Older revision		Revision as of 04:10, 19 June 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6nne is ON HOLD ~~until Paper Publication~~	+	The entry 6nne is ON HOLD

	Authors: Ribeiro, J.A., Chavez-Pacheco, S.M., Dias, M.V.B.		Authors: Ribeiro, J.A., Chavez-Pacheco, S.M., Dias, M.V.B.

OCA at 03:57, 12 June 2019

OCA — Wed, 12 Jun 2019 03:57:24 GMT

←Older revision		Revision as of 03:57, 12 June 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Ribeiro, J.A., Chavez-Pacheco, S.M., Dias, M.V.B.		Authors: Ribeiro, J.A., Chavez-Pacheco, S.M., Dias, M.V.B.

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

OCA — Wed, 30 Jan 2019 06:38:30 GMT

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

←Older revision

Revision as of 06:38, 30 January 2019

OCA: New page: '''Unreleased structure''' The entry 6nne is ON HOLD Authors: Ribeiro, J.A., Chavez-Pacheco, S.M., Dias, M.V.B. Description: Crystal structure of Dihydrofolate reductase from Mycobacte...

OCA — Wed, 30 Jan 2019 06:38:28 GMT

New page: '''Unreleased structure''' The entry 6nne is ON HOLD Authors: Ribeiro, J.A., Chavez-Pacheco, S.M., Dias, M.V.B. Description: Crystal structure of Dihydrofolate reductase from Mycobacte...

New page

'''Unreleased structure'''

The entry 6nne is ON HOLD

Authors: Ribeiro, J.A., Chavez-Pacheco, S.M., Dias, M.V.B.

Description: Crystal structure of Dihydrofolate reductase from Mycobacterium tuberculosis in complex with diaverdine
[[Category: Unreleased Structures]]
[[Category: Ribeiro, J.A]]
[[Category: Dias, M.V.B]]
[[Category: Chavez-Pacheco, S.M]]