2H4J

Sir2-deacetylated peptide (from enzymatic turnover in crystal)

Summary for 2H4J

• Entry DOI: 10.2210/pdb2h4j/pdb
• Related: 2H4F 2H4H
• Descriptor: NAD-dependent deacetylase, Cellular tumor antigen p53, ZINC ION, ... (6 entities in total)
• Functional Keywords: rossmann fold, zn binding domain, hydrolase
• Biological source: Thermotoga maritima; More
• Cellular location: Cytoplasm : Q9WYW0; Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: P04637
• Total number of polymer chains: 2
• Total formula weight: 30457.17

Authors

Hoff, K.G.,Avalos, J.L.,Sens, K.,Wolberger, C. (deposition date: 2006-05-24, release date: 2006-09-05, Last modification date: 2023-08-30)

Primary citation

Hoff, K.G.,Avalos, J.L.,Sens, K.,Wolberger, C.
Insights into the Sirtuin Mechanism from Ternary Complexes Containing NAD(+) and Acetylated Peptide.
Structure, 14:1231-1240, 2006

PubMed Abstract: Sirtuin proteins comprise a unique class of NAD+-dependent protein deacetylases. Although several structures of sirtuins have been determined, the mechanism by which NAD+ cleavage occurs has remained unclear. We report the structures of ternary complexes containing NAD+ and acetylated peptide bound to the bacterial sirtuin Sir2Tm and to a catalytic mutant (Sir2Tm(H116Y)). NAD+ in these structures binds in a conformation different from that seen in previous structures, exposing the alpha face of the nicotinamide ribose to the carbonyl oxygen of the acetyl lysine substrate. The NAD+ conformation is identical in both structures, suggesting that proper coenzyme orientation is not dependent on contacts with the catalytic histidine. We also present the structure of Sir2Tm(H116A) bound to deacteylated peptide and 3'-O-acetyl ADP ribose. Taken together, these structures suggest a mechanism for nicotinamide cleavage in which an invariant phenylalanine plays a central role in promoting formation of the O-alkylamidate reaction intermediate and preventing nicotinamide exchange.

PubMed: 16905097
DOI: 10.1016/j.str.2006.06.006

Experimental method

X-RAY DIFFRACTION (2.1 Å)