3v8e

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[[Image:3v8e.png|left|200px]]
 
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==Crystal structure of the yeast nicotinamidase Pnc1p bound to the inhibitor nicotinaldehyde==
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The line below this paragraph, containing "STRUCTURE_3v8e", creates the "Structure Box" on the page.
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<StructureSection load='3v8e' size='340' side='right'caption='[[3v8e]], [[Resolution|resolution]] 2.71&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3v8e]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V8E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V8E FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.71&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JJJ:S-(PYRIDIN-3-YLCARBONYL)-L-CYSTEINE'>JJJ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_3v8e| PDB=3v8e | SCENE= }}
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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=3v8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v8e OCA], [https://pdbe.org/3v8e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v8e RCSB], [https://www.ebi.ac.uk/pdbsum/3v8e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v8e ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PNC1_YEAST PNC1_YEAST] Catalyzes the deamidation of nicotinamide, an early step in the NAD(+) salvage pathway. Positively regulates SIR2-mediated silencing and longevity by preventing the accumulation of intracellular nicotinamide, an inhibitor of SIR2, during times of stress. Acts also on nicotinyl hydroxamate.<ref>PMID:11816029</ref> <ref>PMID:12736687</ref> <ref>PMID:14729974</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Nicotinamidases catalyze the hydrolysis of nicotinamide to nicotinic acid and ammonia. Nicotinamidases are absent in mammals but function in NAD(+) salvage in many bacteria, yeast, plants, protozoa, and metazoans. We have performed structural and kinetic investigations of the nicotinamidase from Saccharomyces cerevisiae (Pnc1). Steady-state product inhibitor analysis revealed an irreversible reaction in which ammonia is the first product released, followed by nicotinic acid. A series of nicotinamide analogues acting as inhibitors or substrates were examined, revealing that the nicotinamide carbonyl oxygen and ring nitrogen are critical for binding and reactivity. X-ray structural analysis revealed a covalent adduct between nicotinaldehyde and Cys167 of Pnc1 and coordination of the nicotinamide ring nitrogen to the active-site zinc ion. Using this structure as a guide, the function of several residues was probed via mutagenesis and primary (15)N and (13)C kinetic isotope effects (KIEs) on V/K for amide bond hydrolysis. The KIE values of almost all variants were increased, indicating that C-N bond cleavage is at least partially rate limiting; however, a decreased KIE for D51N was indicative of a stronger commitment to catalysis. In addition, KIE values using slower alternate substrates indicated that C-N bond cleavage is at least partially rate limiting with nicotinamide to highly rate limiting with thionicotinamide. A detailed mechanism involving nucleophilic attack of Cys167, followed by elimination of ammonia and then hydrolysis to liberate nicotinic acid, is discussed. These results will aid in the design of mechanism-based inhibitors to target pathogens that rely on nicotinamidase activity.
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===Crystal structure of the yeast nicotinamidase Pnc1p bound to the inhibitor nicotinaldehyde===
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Structural and Kinetic Isotope Effect Studies of Nicotinamidase (Pnc1) from Saccharomyces cerevisiae.,Smith BC, Anderson MA, Hoadley KA, Keck JL, Cleland WW, Denu JM Biochemistry. 2012 Jan 10;51(1):243-56. Epub 2011 Dec 29. PMID:22229411<ref>PMID:22229411</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 3v8e" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 22229411 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_22229411}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Large Structures]]
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[[3v8e]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V8E OCA].
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[[Category: Saccharomyces cerevisiae S288C]]
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[[Category: Denu JM]]
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==Reference==
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[[Category: Hoadley KA]]
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<ref group="xtra">PMID:022229411</ref><references group="xtra"/>
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[[Category: Keck JL]]
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[[Category: Nicotinamidase]]
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[[Category: Smith BC]]
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[[Category: Saccharomyces cerevisiae]]
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[[Category: Denu, J M.]]
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[[Category: Hoadley, K A.]]
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[[Category: Keck, J L.]]
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[[Category: Smith, B C.]]
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[[Category: Hydrolase]]
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Current revision

Crystal structure of the yeast nicotinamidase Pnc1p bound to the inhibitor nicotinaldehyde

PDB ID 3v8e

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