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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
38
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pubmed:dateCreated |
2008-9-16
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pubmed:abstractText |
Sirtuins are NAD (+)-dependent enzymes that deacetylate a variety of cellular proteins and in some cases catalyze protein ADP-ribosyl transfer. The catalytic mechanism of deacetylation is proposed to involve an ADPR-peptidylimidate, whereas the mechanism of ADP-ribosyl transfer to proteins is undetermined. Herein we characterize a Plasmodium falciparum sirtuin that catalyzes deacetylation of histone peptide sequences. Interestingly, the enzyme can also hydrolyze NAD (+). Two mechanisms of hydrolysis were identified and characterized. One is independent of acetyllysine substrate and produces alpha-stereochemistry as established by reaction of methanol which forms alpha-1- O-methyl-ADPR. This reaction is insensitive to nicotinamide inhibition. The second solvolytic mechanism is dependent on acetylated peptide and is proposed to involve the imidate to generate beta-stereochemistry. Stereochemistry was established by isolation of beta-1- O-methyl-ADPR when methanol was added as a cosolvent. This solvolytic reaction was inhibited by nicotinamide, suggesting that nicotinamide and solvent compete for the imidate. These findings establish new reactions of wildtype sirtuins and suggest possible mechanisms for ADP-ribosylation to proteins. These findings also illustrate the potential utility of nicotinamide as a probe for mechanisms of sirtuin-catalyzed ADP-ribosyl transfer.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-11095969,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-11747420,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-12297502,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-12760043,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-12899610,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-13371,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-14522996,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-14592982,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-14604530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-15078167,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-15189148,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-15506920,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-15632193,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-15780941,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-15795229,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-15820675,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-15820676,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-16388603,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-16756498,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-16798089,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-16905097,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-16959573,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-17079682,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-17167475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-17644655,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-17827348,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-18165239,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-18221799,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-209022,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-4362061,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-6298221,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-8573568,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-942051,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-9485425,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-9494110,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18729382-9748331
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1520-4995
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
23
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pubmed:volume |
47
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10227-39
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:18729382-Acetylation,
pubmed-meshheading:18729382-Animals,
pubmed-meshheading:18729382-Histones,
pubmed-meshheading:18729382-Hydrolysis,
pubmed-meshheading:18729382-Lysine,
pubmed-meshheading:18729382-NAD,
pubmed-meshheading:18729382-NAD+ Nucleosidase,
pubmed-meshheading:18729382-Peptides,
pubmed-meshheading:18729382-Plasmodium falciparum,
pubmed-meshheading:18729382-Protozoan Proteins,
pubmed-meshheading:18729382-Sirtuins
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pubmed:year |
2008
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pubmed:articleTitle |
Plasmodium falciparum Sir2 is an NAD+-dependent deacetylase and an acetyllysine-dependent and acetyllysine-independent NAD+ glycohydrolase.
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pubmed:affiliation |
Department of Pharmacology, Weill Cornell College of Medicine, 1300 York Avenue LC216, New York, New York 10065, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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