2h0r
Structure of the Yeast Nicotinamidase Pnc1pStructure of the Yeast Nicotinamidase Pnc1p
Structural highlights
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. Publication Abstract from PubMedThe 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. 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:17382284[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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