3v8e: Difference between revisions

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[[Image:3v8e.png|left|200px]]
==Crystal structure of the yeast nicotinamidase Pnc1p bound to the inhibitor nicotinaldehyde==
<StructureSection load='3v8e' size='340' side='right' caption='[[3v8e]], [[Resolution|resolution]] 2.71&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3V8E FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=JJJ:S-(PYRIDIN-3-YLCARBONYL)-L-CYSTEINE'>JJJ</scene></td></tr>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2h0r|2h0r]]</td></tr>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PNC1, YGL037C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae])</td></tr>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3v8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v8e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3v8e RCSB], [http://www.ebi.ac.uk/pdbsum/3v8e PDBsum]</span></td></tr>
<table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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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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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{{STRUCTURE_3v8e|  PDB=3v8e  |  SCENE=  }}


===Crystal structure of the yeast nicotinamidase Pnc1p bound to the inhibitor nicotinaldehyde===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
 
== References ==
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{{ABSTRACT_PUBMED_22229411}}
 
==About this Structure==
[[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].
 
==Reference==
<ref group="xtra">PMID:022229411</ref><references group="xtra"/>
[[Category: Nicotinamidase]]
[[Category: Nicotinamidase]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae]]

Revision as of 07:43, 5 June 2014

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

3v8e, resolution 2.71Å

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