3JR3

Sir2 bound to acetylated peptide

Summary for 3JR3

• Entry DOI: 10.2210/pdb3jr3/pdb
• Descriptor: NAD-dependent deacetylase, Acetylated Peptide, ZINC ION, ... (4 entities in total)
• Functional Keywords: sir2, deacetylation, nad+, ribosylation, hydrolase, metal-binding, nad
• Biological source: Thermotoga maritima
• Cellular location: Cytoplasm (By similarity): Q9WYW0
• Total number of polymer chains: 2
• Total formula weight: 29733.65

Authors

Hawse, W.F.,Wolberger, C. (deposition date: 2009-09-08, release date: 2009-09-29, Last modification date: 2024-10-30)

Primary citation

Hawse, W.F.,Wolberger, C.
Structure-based mechanism of ADP-ribosylation by sirtuins.
J.Biol.Chem., 284:33654-33661, 2009

PubMed Abstract: Sirtuins comprise a family of enzymes found in all organisms, where they play a role in diverse processes including transcriptional silencing, aging, regulation of transcription, and metabolism. The predominant reaction catalyzed by these enzymes is NAD(+)-dependent lysine deacetylation, although some sirtuins exhibit a weaker ADP-ribosyltransferase activity. Although the Sir2 deacetylation mechanism is well established, much less is known about the Sir2 ADP-ribosylation reaction. We have studied the ADP-ribosylation activity of a bacterial sirtuin, Sir2Tm, and show that acetylated peptides containing arginine or lysine 2 residues C-terminal to the acetyl lysine, the +2 position, are preferentially ADP-ribosylated at the +2 residue. A structure of Sir2Tm bound to the acetylated +2 arginine peptide shows how this arginine could enter the active site and react with a deacetylation reaction intermediate to yield an ADP-ribosylated peptide. The new biochemical and structural studies presented here provide mechanistic insights into the Sir2 ADP-ribosylation reaction and will aid in identifying substrates of this reaction.

PubMed: 19801667
DOI: 10.1074/jbc.M109.024521

Experimental method

X-RAY DIFFRACTION (1.5 Å)