8dsh: Difference between revisions

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-'''Unreleased structure'''
-The entry 8dsh is ON HOLD  until Paper Publication
+==Human NAMPT in complex with quercitrin and AMPcP==
+<StructureSection load='8dsh' size='340' side='right'caption='[[8dsh]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8dsh]] is a 2 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=8DSH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DSH FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A12:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>A12</scene>, <scene name='pdbligand=QCT:2-(3,4-DIHYDROXYPHENYL)-5,7-DIHYDROXY-4-OXO-4H-CHROMEN-3-YL+6-DEOXY-ALPHA-L-MANNOPYRANOSIDE'>QCT</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=8dsh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dsh OCA], [https://pdbe.org/8dsh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dsh RCSB], [https://www.ebi.ac.uk/pdbsum/8dsh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dsh ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+In aging and disease, cellular nicotinamide adenine dinucleotide (NAD(+)) is depleted by catabolism to nicotinamide (NAM). NAD(+) supplementation is being pursued to enhance human healthspan and lifespan. Activation of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD(+) biosynthesis, has the potential to increase the salvage of NAM. Novel NAMPT-positive allosteric modulators (N-PAMs) were discovered in addition to the demonstration of NAMPT activation by biogenic phenols. The mechanism of activation was revealed through the synthesis of novel chemical probes, new NAMPT co-crystal structures, and enzyme kinetics. Binding to a rear channel in NAMPT regulates NAM binding and turnover, with biochemical observations being replicated by NAD(+) measurements in human cells. The mechanism of action of N-PAMs identifies, for the first time, the role of the rear channel in the regulation of NAMPT turnover coupled to productive and nonproductive NAM binding. The tight regulation of cellular NAMPT via feedback inhibition by NAM, NAD(+), and adenosine 5'-triphosphate (ATP) is differentially regulated by N-PAMs and other activators, indicating that different classes of pharmacological activators may be engineered to restore or enhance NAD(+) levels in affected tissues.
-Authors: Ratia, K., Xiong, R., Shen, Z., Thatcher, G.R.
+Mechanism of Allosteric Modulation of Nicotinamide Phosphoribosyltransferase to Elevate Cellular NAD().,Ratia KM, Shen Z, Gordon-Blake J, Lee H, Laham MS, Krider IS, Christie N, Ackerman-Berrier M, Penton C, Knowles NG, Musku SR, Fu J, Velma GR, Xiong R, Thatcher GRJ Biochemistry. 2023 Feb 21;62(4):923-933. doi: 10.1021/acs.biochem.2c00655. Epub , 2023 Feb 6. PMID:36746631<ref>PMID:36746631</ref>
-Description: Human NAMPT in complex with quercitrin and AMPcP
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Thatcher, G.R]]
+<div class="pdbe-citations 8dsh" style="background-color:#fffaf0;"></div>
-[[Category: Ratia, K]]
-[[Category: Xiong, R]]
+==See Also==
-[[Category: Shen, Z]]
+*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Ratia K]]
+[[Category: Shen Z]]
+[[Category: Thatcher GR]]
+[[Category: Xiong R]]