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2gvj

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[[Image:2gvj.gif|left|200px]]
 
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{{Structure
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==Crystal Structure of Human NMPRTase in complex with FK866==
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|PDB= 2gvj |SIZE=350|CAPTION= <scene name='initialview01'>2gvj</scene>, resolution 2.10&Aring;
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<StructureSection load='2gvj' size='340' side='right'caption='[[2gvj]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=DGB:N-[4-(1-BENZOYLPIPERIDIN-4-YL)BUTYL]-3-PYRIDIN-3-YLPROPANAMIDE'>DGB</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>
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<table><tr><td colspan='2'>[[2gvj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GVJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GVJ FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Nicotinamide_phosphoribosyltransferase Nicotinamide phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.12 2.4.2.12] </span>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DGB:(2E)-N-{4-[1-(BENZENECARBONYL)PIPERIDIN-4-YL]BUTYL}-3-(PYRIDIN-3-YL)PROP-2-ENAMIDE'>DGB</scene></td></tr>
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|GENE= NAMPT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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|DOMAIN=
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2gvg|2gvg]]</div></td></tr>
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|RELATEDENTRY=[[2gvg|2GVG]]
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NAMPT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gvj OCA], [http://www.ebi.ac.uk/pdbsum/2gvj PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2gvj RCSB]</span>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Nicotinamide_phosphoribosyltransferase Nicotinamide phosphoribosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.12 2.4.2.12] </span></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2gvj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gvj OCA], [https://pdbe.org/2gvj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gvj RCSB], [https://www.ebi.ac.uk/pdbsum/2gvj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gvj ProSAT]</span></td></tr>
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</table>
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== Function ==
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[[https://www.uniprot.org/uniprot/NAMPT_HUMAN NAMPT_HUMAN]] Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gv/2gvj_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2gvj ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Nicotinamide phosphoribosyltransferase (NMPRTase) has a crucial role in the salvage pathway of NAD+ biosynthesis, and a potent inhibitor of NMPRTase, FK866, can reduce cellular NAD+ levels and induce apoptosis in tumors. We have determined the crystal structures at up to 2.1-A resolution of human and murine NMPRTase, alone and in complex with the reaction product nicotinamide mononucleotide or the inhibitor FK866. The structures suggest that Asp219 is a determinant of substrate specificity of NMPRTase, which is confirmed by our mutagenesis studies. FK866 is bound in a tunnel at the interface of the NMPRTase dimer, and mutations in this binding site can abolish the inhibition by FK866. Contrary to current knowledge, the structures show that FK866 should compete directly with the nicotinamide substrate. Our structural and biochemical studies provide a starting point for the development of new anticancer agents.
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'''Crystal Structure of Human NMPRTase in complex with FK866'''
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Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents.,Khan JA, Tao X, Tong L Nat Struct Mol Biol. 2006 Jul;13(7):582-8. Epub 2006 Jun 18. PMID:16783377<ref>PMID:16783377</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2gvj" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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Nicotinamide phosphoribosyltransferase (NMPRTase) has a crucial role in the salvage pathway of NAD+ biosynthesis, and a potent inhibitor of NMPRTase, FK866, can reduce cellular NAD+ levels and induce apoptosis in tumors. We have determined the crystal structures at up to 2.1-A resolution of human and murine NMPRTase, alone and in complex with the reaction product nicotinamide mononucleotide or the inhibitor FK866. The structures suggest that Asp219 is a determinant of substrate specificity of NMPRTase, which is confirmed by our mutagenesis studies. FK866 is bound in a tunnel at the interface of the NMPRTase dimer, and mutations in this binding site can abolish the inhibition by FK866. Contrary to current knowledge, the structures show that FK866 should compete directly with the nicotinamide substrate. Our structural and biochemical studies provide a starting point for the development of new anticancer agents.
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*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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2GVJ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GVJ OCA].
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__TOC__
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</StructureSection>
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==Reference==
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[[Category: Human]]
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Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents., Khan JA, Tao X, Tong L, Nat Struct Mol Biol. 2006 Jul;13(7):582-8. Epub 2006 Jun 18. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16783377 16783377]
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[[Category: Large Structures]]
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[[Category: Homo sapiens]]
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[[Category: Nicotinamide phosphoribosyltransferase]]
[[Category: Nicotinamide phosphoribosyltransferase]]
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[[Category: Single protein]]
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[[Category: Khan, J A]]
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[[Category: Khan, J A.]]
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[[Category: Tao, X]]
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[[Category: Tao, X.]]
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[[Category: Tong, L]]
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[[Category: Tong, L.]]
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[[Category: Cancer]]
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[[Category: cancer]]
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[[Category: Fk866]]
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[[Category: fk866]]
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[[Category: Nmprtase]]
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[[Category: nmprtase]]
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[[Category: Pbef]]
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[[Category: pbef]]
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[[Category: Transferase]]
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[[Category: visfatin]]
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[[Category: Visfatin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:22:11 2008''
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Current revision

Crystal Structure of Human NMPRTase in complex with FK866

PDB ID 2gvj

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