Abstract
The SIR2 protein family comprises a novel class of nicotinamide-adenine dinucleotide (NAD)-dependent protein deacetylases that function in transcriptional silencing, DNA repair, and life-span extension in Saccharomyces cerevisiae. Two crystal structures of a SIR2 homolog from Archaeoglobus fulgidus complexed with NAD have been determined at 2.1 A and 2.4 A resolutions. The structures reveal that the protein consists of a large domain having a Rossmann fold and a small domain containing a three-stranded zinc ribbon motif. NAD is bound in a pocket between the two domains. A distinct mode of NAD binding and an unusual configuration of the zinc ribbon motif are observed. The structures also provide important insights into the catalytic mechanism of NAD-dependent protein deacetylation by this family of enzymes.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Archaeal Proteins / chemistry*
-
Archaeal Proteins / genetics
-
Archaeal Proteins / metabolism
-
Archaeoglobus fulgidus / chemistry*
-
Archaeoglobus fulgidus / genetics
-
Binding Sites
-
Crystallography, X-Ray
-
Histone Deacetylases / chemistry*
-
Histone Deacetylases / genetics
-
Histone Deacetylases / metabolism
-
Models, Molecular
-
Molecular Sequence Data
-
NAD / chemistry*
-
NAD / metabolism
-
Protein Structure, Tertiary*
-
Sequence Alignment
-
Silent Information Regulator Proteins, Saccharomyces cerevisiae*
-
Sirtuin 2
-
Sirtuins
-
Trans-Activators / chemistry*
-
Trans-Activators / genetics
-
Trans-Activators / metabolism
Substances
-
Archaeal Proteins
-
Silent Information Regulator Proteins, Saccharomyces cerevisiae
-
Trans-Activators
-
NAD
-
SIR2 protein, S cerevisiae
-
Sirtuin 2
-
Sirtuins
-
Histone Deacetylases