7et7 - Revision history

OCA at 17:02, 29 November 2023

2023-11-29T17:02:09Z

←Older revision		Revision as of 17:02, 29 November 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7et7]] 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=7ET7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ET7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[7et7]] 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=7ET7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ET7 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JCU:10-methyl-1,10-diazatricyclo[6.3.1.0^{4,12}]dodeca-4,6,8(12)-trien-11-imine'>JCU</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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]] 2.61Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JCU:10-methyl-1,10-diazatricyclo[6.3.1.0^{4,12}]dodeca-4,6,8(12)-trien-11-imine'>JCU</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=7et7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7et7 OCA], [https://pdbe.org/7et7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7et7 RCSB], [https://www.ebi.ac.uk/pdbsum/7et7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7et7 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=7et7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7et7 OCA], [https://pdbe.org/7et7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7et7 RCSB], [https://www.ebi.ac.uk/pdbsum/7et7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7et7 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 10:52, 30 November 2022

2022-11-30T10:52:37Z

←Older revision		Revision as of 10:52, 30 November 2022
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	==Co-crystal structure of Human Nicotinamide N-methyltransferase (NNMT) with tricyclic small molecule inhibitor JBSNF-000028==		==Co-crystal structure of Human Nicotinamide N-methyltransferase (NNMT) with tricyclic small molecule inhibitor JBSNF-000028==
-	<StructureSection load='7et7' size='340' side='right'caption='[[7et7]]' scene=''>	+	<StructureSection load='7et7' size='340' side='right'caption='[[7et7]], [[Resolution\|resolution]] 2.61Å' 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=7ET7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ET7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7et7]] 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=7ET7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ET7 FirstGlance]. <br>
-	</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=7et7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7et7 OCA], [https://pdbe.org/7et7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7et7 RCSB], [https://www.ebi.ac.uk/pdbsum/7et7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7et7 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JCU:10-methyl-1,10-diazatricyclo[6.3.1.0^{4,12}]dodeca-4,6,8(12)-trien-11-imine'>JCU</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=7et7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7et7 OCA], [https://pdbe.org/7et7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7et7 RCSB], [https://www.ebi.ac.uk/pdbsum/7et7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7et7 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[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.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Nicotinamide N-methyltransferase (NNMT) is a metabolic regulator that catalyzes the methylation of nicotinamide (Nam) using the co-factor S-adenosyl-L-methionine to form 1-methyl-nicotinamide (MNA). Overexpression of NNMT and the presence of the active metabolite MNA is associated with a number of diseases including metabolic disorders. We conducted a high-throughput screening campaign that led to the identification of a tricyclic core as a potential NNMT small molecule inhibitor series. Elaborate medicinal chemistry efforts were undertaken and hundreds of analogs were synthesized to understand the structure activity relationship and structure property relationship of this tricyclic series. A lead molecule, JBSNF-000028, was identified that inhibits human and mouse NNMT activity, reduces MNA levels in mouse plasma, liver and adipose tissue, and drives insulin sensitization, glucose modulation and body weight reduction in a diet-induced obese mouse model of diabetes. The co-crystal structure showed that JBSNF-000028 binds below a hairpin structural motif at the nicotinamide pocket and stacks between Tyr-204 (from Hairpin) and Leu-164 (from central domain). JBSNF-000028 was inactive against a broad panel of targets related to metabolism and safety. Interestingly, the improvement in glucose tolerance upon treatment with JBSNF-000028 was also observed in NNMT knockout mice with diet-induced obesity, pointing towards the glucose-normalizing effect that may go beyond NNMT inhibition. JBSNF-000028 can be a potential therapeutic option for metabolic disorders and developmental studies are warranted.
		+
		+	Novel tricyclic small molecule inhibitors of Nicotinamide N-methyltransferase for the treatment of metabolic disorders.,Ruf S, Rajagopal S, Kadnur SV, Hallur MS, Rani S, Kristam R, Swaminathan S, Zope BR, Gondrala PK, Swamy I, Putta VPRK, Kandan S, Zech G, Schreuder H, Rudolph C, Elvert R, Czech J, Birudukota S, Siddiqui MA, Anand NN, Mane VS, Dittakavi S, Suresh J, Gosu R, Ramesh M, Yura T, Dhakshinamoorthy S, Kannt A Sci Rep. 2022 Sep 14;12(1):15440. doi: 10.1038/s41598-022-19634-2. PMID:36104373<ref>PMID:36104373</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7et7" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Birudukota S]]		[[Category: Birudukota S]]

OCA at 10:13, 18 May 2022

2022-05-18T10:13:57Z

←Older revision		Revision as of 10:13, 18 May 2022
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-	'''Unreleased structure'''

-	~~The entry 7et7 is ON HOLD until Paper Publication~~	+	==Co-crystal structure of Human Nicotinamide N-methyltransferase (NNMT) with tricyclic small molecule inhibitor JBSNF-000028==
-		+	<StructureSection load='7et7' size='340' side='right'caption='[[7et7]]' scene=''>
-	~~Authors: Swaminathan, S., Gosu, R., Birudukota, S., Kandan, S., Vaithilingam, K.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ET7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ET7 FirstGlance]. <br>
-	~~Description:~~ Co-crystal structure of Human Nicotinamide N-methyltransferase (NNMT) with tricyclic small molecule inhibitor JBSNF-000028	+	</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=7et7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7et7 OCA], [https://pdbe.org/7et7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7et7 RCSB], [https://www.ebi.ac.uk/pdbsum/7et7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7et7 ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Swaminathan~~, S]]	+	__TOC__
-	[[Category: ~~Kandan, S~~]]	+	</StructureSection>
-	[[Category: Birudukota, S]]	+	[[Category: Large Structures]]
-	[[Category: Gosu, R]]	+	[[Category: Birudukota S]]
-	[[Category: Vaithilingam, K]]	+	[[Category: Gosu R]]
		+	[[Category: Kandan S]]
		+	[[Category: Swaminathan S]]
		+	[[Category: Vaithilingam K]]

OCA at 07:48, 26 May 2021

2021-05-26T07:48:53Z

←Older revision		Revision as of 07:48, 26 May 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7et7 is ON HOLD	+	The entry 7et7 is ON HOLD until Paper Publication

	Authors: Swaminathan, S., Gosu, R., Birudukota, S., Kandan, S., Vaithilingam, K.		Authors: Swaminathan, S., Gosu, R., Birudukota, S., Kandan, S., Vaithilingam, K.
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	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Swaminathan, S]]		[[Category: Swaminathan, S]]
-	[[Category: Vaithilingam, K]]
	[[Category: Kandan, S]]		[[Category: Kandan, S]]
	[[Category: Birudukota, S]]		[[Category: Birudukota, S]]
	[[Category: Gosu, R]]		[[Category: Gosu, R]]
		+	[[Category: Vaithilingam, K]]

OCA: Protected "7et7" [edit=sysop:move=sysop]

2021-05-19T08:46:59Z

Protected "7et7" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:46, 19 May 2021

OCA: New page: '''Unreleased structure''' The entry 7et7 is ON HOLD Authors: Swaminathan, S., Gosu, R., Birudukota, S., Kandan, S., Vaithilingam, K. Description: Co-crystal structure of Human Nicotin...

2021-05-19T08:46:57Z

New page: '''Unreleased structure''' The entry 7et7 is ON HOLD Authors: Swaminathan, S., Gosu, R., Birudukota, S., Kandan, S., Vaithilingam, K. Description: Co-crystal structure of Human Nicotin...

New page

'''Unreleased structure'''

The entry 7et7 is ON HOLD

Authors: Swaminathan, S., Gosu, R., Birudukota, S., Kandan, S., Vaithilingam, K.

Description: Co-crystal structure of Human Nicotinamide N-methyltransferase (NNMT) with tricyclic small molecule inhibitor JBSNF-000028
[[Category: Unreleased Structures]]
[[Category: Swaminathan, S]]
[[Category: Vaithilingam, K]]
[[Category: Kandan, S]]
[[Category: Birudukota, S]]
[[Category: Gosu, R]]