1Q17

Structure of the yeast Hst2 protein deacetylase in ternary complex with 2'-O-acetyl ADP ribose and histone peptide

Summary for 1Q17

• Entry DOI: 10.2210/pdb1q17/pdb
• Related: 1Q14
• Descriptor: HST2 protein, ZINC ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: histone deacetylase, hydrolase
• Biological source: Saccharomyces cerevisiae (baker's yeast)
• Cellular location: Nucleus (Potential): P53686
• Total number of polymer chains: 3
• Total formula weight: 103445.18

Authors

Zhao, K.,Chai, X.,Marmorstein, R. (deposition date: 2003-07-18, release date: 2003-11-18, Last modification date: 2023-08-16)

Primary citation

Zhao, K.,Chai, X.,Marmorstein, R.
Structure of the Yeast Hst2 Protein Deacetylase in Ternary Complex with 2'-O-Acetyl ADP Ribose and Histone Peptide.
Structure, 11:1403-1411, 2003

PubMed Abstract: Sir2 proteins are NAD(+)-dependant protein deactylases that have been implicated in playing roles in gene silencing, DNA repair, genome stability, longevity, metabolism, and cell physiology. To define the mechanism of Sir2 activity, we report the 1.5 A crystal structure of the yeast Hst2 (yHst2) Sir2 protein in ternary complex with 2'-O-acetyl ADP ribose and an acetylated histone H4 peptide. The structure captures both ligands meeting within an enclosed tunnel between the small and large domains of the catalytic protein core and permits the assignment of a detailed catalytic mechanism for the Sir2 proteins that is consistent with solution and enzymatic studies. Comparison of the ternary complex with the yHst2/NAD(+) complex, also reported here, and nascent yHst2 structure also reveals that NAD(+) binding accompanies intramolecular loop rearrangement for more stable NAD(+) and acetyl-lysine binding, and that acetyl-lysine peptide binding induces a trimer-monomer protein transition involving nonconserved Sir2 residues.

PubMed: 14604530
DOI: 10.1016/j.str.2003.09.016

Experimental method

X-RAY DIFFRACTION (2.7 Å)