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| - | | + | #REDIRECT [[6chh]] This PDB entry is obsolete and replaced by 6chh |
| - | ==Structure of human NNMT in complex with bisubstrate inhibitor MS2756==
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| - | <StructureSection load='6b1a' size='340' side='right'caption='[[6b1a]], [[Resolution|resolution]] 2.30Å' scene=''>
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| - | == Structural highlights ==
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| - | <table><tr><td colspan='2'>[[6b1a]] 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=6B1A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B1A FirstGlance]. <br>
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| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C8J:(2~{R})-5-[2-(3-aminocarbonylphenyl)ethyl-[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl]amino]-2-azanyl-pentanoic+acid'>C8J</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
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| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NNMT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nicotinamide_N-methyltransferase Nicotinamide N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.1 2.1.1.1] </span></td></tr>
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| - | <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=6b1a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b1a OCA], [http://pdbe.org/6b1a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b1a RCSB], [http://www.ebi.ac.uk/pdbsum/6b1a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b1a ProSAT]</span></td></tr>
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| - | </table>
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| - | == Function ==
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| - | [[http://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.
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| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of pyridine-containing compounds using the cofactor S-5'-adenosyl-L-methionine (SAM) as the methyl group donor. Through the regulation of the levels of its substrates, cofactor, and products, NNMT plays important role in physiology and pathophysiology. Overexpression of NNMT has been implicated in various human diseases. Potent and selective small-molecule NNMT inhibitors are valuable chemical tools for testing biological and therapeutic hypotheses. However, very few NNMT inhibitors have been reported. Here, we describe the discovery of a bisubstrate NNMT inhibitor MS2734 (6), and characterization of this inhibitor in biochemical, biophysical, kinetic, and structural studies. Importantly, we obtained the first crystal structure of human NNMT in complex with a small-molecule inhibitor. The structure of the NNMT-6 complex has unambiguously demonstrated that 6 occupied both substrate and cofactor binding sites. The findings paved the way for developing more potent and selective NNMT inhibitors in the future.
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| - | Discovery of Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT).,Babault N, Allali-Hassani A, Li F, Fan J, Yue A, Ju K, Liu F, Vedadi M, Liu J, Jin J J Med Chem. 2018 Jan 10. doi: 10.1021/acs.jmedchem.7b01422. PMID:29320176<ref>PMID:29320176</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 6b1a" style="background-color:#fffaf0;"></div>
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| - | == References ==
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| - | <references/>
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| - | __TOC__
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| - | </StructureSection>
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| - | [[Category: Human]]
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| - | [[Category: Large Structures]]
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| - | [[Category: Nicotinamide N-methyltransferase]]
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| - | [[Category: Babault, N]]
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| - | [[Category: Jin, J]]
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| - | [[Category: Liu, J]]
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| - | [[Category: Protein-small molecule bisubstrate inhibitor complex]]
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| - | [[Category: Transferase]]
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| - | [[Category: Transferase-transferase inhibitor complex]]
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