6pve - Revision history

OCA at 14:55, 13 March 2024

OCA — Wed, 13 Mar 2024 14:55:35 GMT

←Older revision		Revision as of 14:55, 13 March 2024
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	<StructureSection load='6pve' size='340' side='right'caption='[[6pve]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='6pve' size='340' side='right'caption='[[6pve]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6pve]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PVE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6PVE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6pve]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PVE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PVE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OZP:9-(5-{[(3S)-3-amino-3-carboxypropyl][3-(3-carbamoylphenyl)propyl]amino}-5-deoxy-alpha-D-ribofuranosyl)-9H-purin-6-amine'>OZP</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]] 2.3Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NNMT, hCG_39357 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OZP:9-(5-{[(3S)-3-amino-3-carboxypropyl][3-(3-carbamoylphenyl)propyl]amino}-5-deoxy-alpha-D-ribofuranosyl)-9H-purin-6-amine'>OZP</scene></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=6pve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pve OCA], [~~http~~://pdbe.org/6pve PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6pve RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6pve PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6pve ProSAT]</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=6pve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pve OCA], [https://pdbe.org/6pve PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pve RCSB], [https://www.ebi.ac.uk/pdbsum/6pve PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pve ProSAT]</span></td></tr>
	</table>		</table>
-	~~<div style="background-color:#fffaf0;">~~	+	== Function ==
-	== ~~Publication Abstract from PubMed~~ ==	+	[https://www.uniprot.org/uniprot/NNMT_HUMAN NNMT_HUMAN] Catalyzes the N-methylation of nicotinamide and other pyridines to form pyridinium ions. This activity is important for biotransformation of many drugs and xenobiotic compounds.
-	~~Nicotinamide~~ N-~~methyltransferase (NNMT) catalyzes the methyl transfer from cofactor S-adenosylmethionine (SAM) to~~ nicotinamide and other ~~pyridine-containing compounds~~. ~~NNMT~~ is an important ~~regulator~~ for ~~nicotinamide metabolism and methylation potential. Aberrant expression levels~~ of ~~NNMT have been implicated in cancer, metabolic~~ and ~~neurodegenerative diseases, which makes NNMT a potential therapeutic target~~. Therefore, potent and selective NNMT inhibitors can serve as valuable tools to investigate the roles of NNMT in its mediated diseases. Here, we applied a rational strategy to design and synthesize the tight-binding bisubstrate inhibitor LL320 through a novel propargyl linker. LL320 demonstrates a Ki value of 1.6+/-0.3 nM, which is the most potent inhibitor to date. The co-crystal structure of LL320 confirms its interaction with both the substrate and cofactor binding sites on NNMT. Importantly, this is the first example of using propargyl linker to construct potent methyltransferase inhibitors, which will expand our understanding of the transition state of methyl transfer.	+
-		+
-	Novel Propargyl-linked Bisubstrate Analogs as Tight-binding Inhibitors for Nicotinamide N-Methyltransferase.,Chen D, Li L, Diaz K, Iyamu ID, Yadav R, Noinaj N, Huang R J Med Chem. 2019 Nov 14. doi: 10.1021/acs.jmedchem.9b01255. PMID:31724854<ref>PMID:31724854</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6pve" style="background-color:#fffaf0;"></div>~~	+
-	~~== References ==~~	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Chen, D]]	+	[[Category: Chen D]]
-	[[Category: Huang, R]]	+	[[Category: Huang R]]
-	[[Category: Noinaj, N]]	+	[[Category: Noinaj N]]
-	[[Category: Yadav, R]]	+	[[Category: Yadav R]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Methyltransferase]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 12:34, 18 December 2019

OCA — Wed, 18 Dec 2019 12:34:21 GMT

←Older revision		Revision as of 12:34, 18 December 2019
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	<StructureSection load='6pve' size='340' side='right'caption='[[6pve]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='6pve' size='340' side='right'caption='[[6pve]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6pve]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PVE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PVE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6pve]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PVE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PVE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OZP:9-(5-{[(3S)-3-amino-3-carboxypropyl][3-(3-carbamoylphenyl)propyl]amino}-5-deoxy-alpha-D-ribofuranosyl)-9H-purin-6-amine'>OZP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OZP:9-(5-{[(3S)-3-amino-3-carboxypropyl][3-(3-carbamoylphenyl)propyl]amino}-5-deoxy-alpha-D-ribofuranosyl)-9H-purin-6-amine'>OZP</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NNMT, hCG_39357 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6pve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pve OCA], [http://pdbe.org/6pve PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pve RCSB], [http://www.ebi.ac.uk/pdbsum/6pve PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pve 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=6pve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pve OCA], [http://pdbe.org/6pve PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pve RCSB], [http://www.ebi.ac.uk/pdbsum/6pve PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pve ProSAT]</span></td></tr>
	</table>		</table>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Chen, D]]		[[Category: Chen, D]]

OCA at 06:53, 27 November 2019

OCA — Wed, 27 Nov 2019 06:53:39 GMT

←Older revision		Revision as of 06:53, 27 November 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6pve is ~~ON HOLD until Paper~~ Publication	+	==Structure of Nicotinamide N-Methyltransferase (NNMT) in complex with inhibitor LL319==
		+	<StructureSection load='6pve' size='340' side='right'caption='[[6pve]], [[Resolution\|resolution]] 2.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6pve]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PVE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PVE FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OZP:9-(5-{[(3S)-3-amino-3-carboxypropyl][3-(3-carbamoylphenyl)propyl]amino}-5-deoxy-alpha-D-ribofuranosyl)-9H-purin-6-amine'>OZP</scene></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=6pve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pve OCA], [http://pdbe.org/6pve PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pve RCSB], [http://www.ebi.ac.uk/pdbsum/6pve PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pve ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Nicotinamide N-methyltransferase (NNMT) catalyzes the methyl transfer from cofactor S-adenosylmethionine (SAM) to nicotinamide and other pyridine-containing compounds. NNMT is an important regulator for nicotinamide metabolism and methylation potential. Aberrant expression levels of NNMT have been implicated in cancer, metabolic and neurodegenerative diseases, which makes NNMT a potential therapeutic target. Therefore, potent and selective NNMT inhibitors can serve as valuable tools to investigate the roles of NNMT in its mediated diseases. Here, we applied a rational strategy to design and synthesize the tight-binding bisubstrate inhibitor LL320 through a novel propargyl linker. LL320 demonstrates a Ki value of 1.6+/-0.3 nM, which is the most potent inhibitor to date. The co-crystal structure of LL320 confirms its interaction with both the substrate and cofactor binding sites on NNMT. Importantly, this is the first example of using propargyl linker to construct potent methyltransferase inhibitors, which will expand our understanding of the transition state of methyl transfer.

-	~~Authors~~:	+	Novel Propargyl-linked Bisubstrate Analogs as Tight-binding Inhibitors for Nicotinamide N-Methyltransferase.,Chen D, Li L, Diaz K, Iyamu ID, Yadav R, Noinaj N, Huang R J Med Chem. 2019 Nov 14. doi: 10.1021/acs.jmedchem.9b01255. PMID:31724854<ref>PMID:31724854</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6pve" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Chen, D]]
		+	[[Category: Huang, R]]
		+	[[Category: Noinaj, N]]
		+	[[Category: Yadav, R]]
		+	[[Category: Inhibitor]]
		+	[[Category: Methyltransferase]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 13:45, 28 August 2019

OCA — Wed, 28 Aug 2019 13:45:33 GMT

←Older revision		Revision as of 13:45, 28 August 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 31 Jul 2019 04:46:16 GMT

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

←Older revision

Revision as of 04:46, 31 July 2019

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

OCA — Wed, 31 Jul 2019 04:46:14 GMT

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

New page

'''Unreleased structure'''

The entry 6pve is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]