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[[Image:2h0r.gif|left|200px]]


{{Structure
==Structure of the Yeast Nicotinamidase Pnc1p==
|PDB= 2h0r |SIZE=350|CAPTION= <scene name='initialview01'>2h0r</scene>, resolution 2.90&Aring;
<StructureSection load='2h0r' size='340' side='right'caption='[[2h0r]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
<table><tr><td colspan='2'>[[2h0r]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H0R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H0R FirstGlance]. <br>
|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Nicotinamidase Nicotinamidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.19 3.5.1.19] </span>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2h0r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h0r OCA], [https://pdbe.org/2h0r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h0r RCSB], [https://www.ebi.ac.uk/pdbsum/2h0r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h0r ProSAT]</span></td></tr>
|RELATEDENTRY=
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2h0r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h0r OCA], [http://www.ebi.ac.uk/pdbsum/2h0r PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2h0r RCSB]</span>
== Function ==
}}
[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>
 
== Evolutionary Conservation ==
'''Structure of the Yeast Nicotinamidase Pnc1p'''
[[Image:Consurf_key_small.gif|200px|right]]
 
Check<jmol>
 
  <jmolCheckbox>
==Overview==
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h0/2h0r_consurf.spt"</scriptWhenChecked>
The yeast nicotinamidase Pnc1p acts in transcriptional silencing by reducing levels of nicotinamide, an inhibitor of the histone deacetylase Sir2p. The Pnc1p structure was determined at 2.9A resolution using MAD and MIRAS phasing methods after inadvertent crystallization during the pursuit of the structure of histidine-tagged yeast isocitrate dehydrogenase (IDH). Pnc1p displays a cluster of surface histidine residues likely responsible for its co-fractionation with IDH from Ni(2+)-coupled chromatography resins. Researchers expressing histidine-tagged proteins in yeast should be aware of the propensity of Pnc1p to crystallize, even when overwhelmed in concentration by the protein of interest. The protein assembles into extended helical arrays interwoven to form an unusually robust, yet porous superstructure. Comparison of the Pnc1p structure with those of three homologous bacterial proteins reveals a common core fold punctuated by amino acid insertions unique to each protein. These insertions mediate the self-interactions that define the distinct higher order oligomeric states attained by these molecules. Pnc1p also acts on pyrazinamide, a substrate analog converted by the nicotinamidase from Mycobacterium tuberculosis into a product toxic to that organism. However, we find no evidence for detrimental effects of the drug on yeast cell growth.
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 
    <text>to colour the structure by Evolutionary Conservation</text>
==About this Structure==
  </jmolCheckbox>
2H0R is a [[Single protein]] structure of 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=2H0R OCA].  
</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=2h0r ConSurf].
 
<div style="clear:both"></div>
==Reference==
== References ==
Crystal structure of the yeast nicotinamidase Pnc1p., Hu G, Taylor AB, McAlister-Henn L, Hart PJ, Arch Biochem Biophys. 2007 May 1;461(1):66-75. Epub 2007 Mar 2. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17382284 17382284]
<references/>
[[Category: Nicotinamidase]]
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Single protein]]
[[Category: Hart PJ]]
[[Category: Hart, P J.]]
[[Category: Hu G]]
[[Category: Hu, G.]]
[[Category: McAlister-Henn L]]
[[Category: McAlister-Henn, L.]]
[[Category: Taylor AB]]
[[Category: Taylor, A B.]]
[[Category: nad+ salvage pathway]]
[[Category: nicotinamidase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:23:49 2008''

Latest revision as of 12:30, 14 February 2024

Structure of the Yeast Nicotinamidase Pnc1pStructure of the Yeast Nicotinamidase Pnc1p

Structural highlights

2h0r is a 7 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.9Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1] [2] [3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

  1. ↑ Ghislain M, Talla E, Francois JM. Identification and functional analysis of the Saccharomyces cerevisiae nicotinamidase gene, PNC1. Yeast. 2002 Feb;19(3):215-24. PMID:11816029 doi:http://dx.doi.org/10.1002/yea.810
  2. ↑ Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Sinclair DA. Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature. 2003 May 8;423(6936):181-5. PMID:12736687 doi:http://dx.doi.org/10.1038/nature01578
  3. ↑ Gallo CM, Smith DL Jr, Smith JS. Nicotinamide clearance by Pnc1 directly regulates Sir2-mediated silencing and longevity. Mol Cell Biol. 2004 Feb;24(3):1301-12. PMID:14729974

2h0r, resolution 2.90Å

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