6pvs: Difference between revisions

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<StructureSection load='6pvs' size='340' side='right'caption='[[6pvs]], [[Resolution|resolution]] 2.58&Aring;' scene=''>
<StructureSection load='6pvs' size='340' side='right'caption='[[6pvs]], [[Resolution|resolution]] 2.58&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6pvs]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PVS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PVS FirstGlance]. <br>
<table><tr><td colspan='2'>[[6pvs]] 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=6PVS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PVS FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P0V:9-(5-{[(3R)-3-amino-3-carboxypropyl][3-(3-carbamoylphenyl)prop-2-yn-1-yl]amino}-5-deoxy-alpha-D-lyxofuranosyl)-9H-purin-6-amine'>P0V</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]] 2.575&#8491;</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=6pvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pvs OCA], [http://pdbe.org/6pvs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pvs RCSB], [http://www.ebi.ac.uk/pdbsum/6pvs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pvs ProSAT]</span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P0V:9-(5-{[(3R)-3-amino-3-carboxypropyl][3-(3-carbamoylphenyl)prop-2-yn-1-yl]amino}-5-deoxy-alpha-D-lyxofuranosyl)-9H-purin-6-amine'>P0V</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=6pvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pvs OCA], [https://pdbe.org/6pvs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pvs RCSB], [https://www.ebi.ac.uk/pdbsum/6pvs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pvs 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6pvs" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[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]]

Latest revision as of 17:55, 13 March 2024

Structure of Nicotinamide N-Methyltransferase (NNMT) in complex with inhibitor LL320Structure of Nicotinamide N-Methyltransferase (NNMT) in complex with inhibitor LL320

Structural highlights

6pvs is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.575Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.

6pvs, resolution 2.58Å

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OCA
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