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[[Image:2h0r.gif|left|200px]]<br /><applet load="2h0r" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2h0r, resolution 2.90&Aring;" />
'''Structure of the Yeast Nicotinamidase Pnc1p'''<br />


==Overview==
==Structure of the Yeast Nicotinamidase Pnc1p==
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.
<StructureSection load='2h0r' size='340' side='right'caption='[[2h0r]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<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>
2H0R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H0R OCA].
</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>
 
<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>
==Reference==
<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>
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://ispc.weizmann.ac.il//pmbin/getpm?pmid=17382284 17382284]
</table>
[[Category: Nicotinamidase]]
== 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 ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h0/2h0r_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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>
== References ==
<references/>
__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: ZN]]
[[Category: nad+ salvage pathway]]
[[Category: nicotinamidase]]
 
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