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| ==Crystal Structure of Visfatin/Pre-B Cell Colony Enhancing Factor 1/Nicotinamide Phosphoribosyltransferase== | | ==Crystal Structure of Visfatin/Pre-B Cell Colony Enhancing Factor 1/Nicotinamide Phosphoribosyltransferase== |
| <StructureSection load='2g95' size='340' side='right' caption='[[2g95]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='2g95' size='340' side='right'caption='[[2g95]], [[Resolution|resolution]] 1.90Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[2g95]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G95 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2G95 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2g95]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G95 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2G95 FirstGlance]. <br> |
| </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2g96|2g96]], [[2g97|2g97]]</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]] 1.9Å</td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></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=2g95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g95 OCA], [https://pdbe.org/2g95 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2g95 RCSB], [https://www.ebi.ac.uk/pdbsum/2g95 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2g95 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=2g95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g95 OCA], [http://pdbe.org/2g95 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2g95 RCSB], [http://www.ebi.ac.uk/pdbsum/2g95 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2g95 ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/NAMPT_RAT NAMPT_RAT]] 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). | | [https://www.uniprot.org/uniprot/NAMPT_RAT NAMPT_RAT] 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). |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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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=2g95 ConSurf]. | | </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=2g95 ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Visfatin/pre-B cell colony-enhancing factor 1 (PBEF)/nicotinamide phosphoribosyltransferase (NAmPRTase) is a multifunctional protein having phosphoribosyltransferase, cytokine and adipokine activities. Originally isolated as a cytokine promoting the differentiation of B cell precursors, it was recently suggested to act as an insulin analog via the insulin receptor. Here, we describe the first crystal structure of visfatin in three different forms: apo and in complex with either nicotinamide mononucleotide (NMN) or the NAmPRTase inhibitor FK-866 which was developed as an anti-cancer agent, interferes with NAD biosynthesis, showing a particularly high specificity for NAmPRTase. The crystal structures of the complexes with either NMN or FK-866 show that the enzymatic active site of visfatin is optimized for nicotinamide binding and that the nicotinamide-binding site is important for inhibition by FK-866. Interestingly, visfatin mimics insulin signaling by binding to the insulin receptor with an affinity similar to that of insulin and does not share the binding site with insulin on the insulin receptor. To predict binding sites, the potential interaction patches of visfatin and the L1-CR-L2 domain of insulin receptor were generated and analyzed. Although the relationship between the insulin-mimetic property and the enzymatic function of visfatin has not been clearly established, our structures raise the intriguing possibility that the glucose metabolism and the NAD biosynthesis are linked by visfatin.
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| Crystal structure of visfatin/pre-B cell colony-enhancing factor 1/nicotinamide phosphoribosyltransferase, free and in complex with the anti-cancer agent FK-866.,Kim MK, Lee JH, Kim H, Park SJ, Kim SH, Kang GB, Lee YS, Kim JB, Kim KK, Suh SW, Eom SH J Mol Biol. 2006 Sep 8;362(1):66-77. Epub 2006 Aug 9. PMID:16901503<ref>PMID:16901503</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 2g95" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Phosphoribosyltransferase|Phosphoribosyltransferase]] | | *[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Buffalo rat]] | | [[Category: Large Structures]] |
| [[Category: Nicotinamide phosphoribosyltransferase]]
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| [[Category: Eom, S H]]
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| [[Category: Kim, M K]]
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| [[Category: Namprtase]]
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| [[Category: Pbef]]
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| [[Category: Rattus norvegicus]] | | [[Category: Rattus norvegicus]] |
| [[Category: Transferase]] | | [[Category: Eom SH]] |
| [[Category: Visfatin]] | | [[Category: Kim M-K]] |