1S5P

Structure and substrate binding properties of cobB, a Sir2 homolog protein deacetylase from Eschericia coli.

Summary for 1S5P

• Entry DOI: 10.2210/pdb1s5p/pdb
• Descriptor: NAD-dependent deacetylase, HISTONE H4 (RESIDUES 12-19), ZINC ION, ... (4 entities in total)
• Functional Keywords: protein deacetylase, sir2 homologue, hydrolase
• Biological source: Escherichia coli; More
• Cellular location: Cytoplasm (Probable): P75960
• Total number of polymer chains: 2
• Total formula weight: 27109.14

Authors

Zhao, K.,Chai, X.,Marmorstein, R. (deposition date: 2004-01-21, release date: 2004-03-23, Last modification date: 2024-10-09)

Primary citation

Zhao, K.,Chai, X.,Marmorstein, R.
Structure and Substrate Binding Properties of cobB, a Sir2 Homolog Protein Deacetylase from Eschericia coli.
J.Mol.Biol., 337:731-741, 2004

PubMed Abstract: Sirtuins are NAD+-dependent protein deacetylase enzymes that are broadly conserved from bacteria to human, and have been implicated to play important roles in gene regulation, metabolism and longevity. cobB is a bacterial sirtuin that deacetylates acetyl-CoA synthetase (Acs) at an active site lysine to stimulate its enzymatic activity. Here, we report the structure of cobB bound to an acetyl-lysine containing non-cognate histone H4 substrate. A comparison with the previously reported archaeal and eukaryotic sirtuin structures reveals the greatest variability in a small zinc-binding domain implicated to play a particularly important role in substrate-specific binding by the sirtuin proteins. Comparison of the cobB/histone H4 complex with other sirtuin proteins in complex with acetyl-lysine containing substrates, further suggests that contacts to the acetyl-lysine side-chain and beta-sheet interactions with residues directly C-terminal to the acetyl-lysine represent conserved features of sirtuin-substrate recognition. Isothermal titration calorimetry studies were used to compare the affinity of cobB for a variety of cognate and non-cognate acetyl-lysine-bearing peptides revealing an exothermic reaction with relatively little discrimination between substrates. In contrast, similar studies employing intact acetylated Acs protein as a substrate reveal a binding reaction that is endothermic, suggesting that cobB recognition of substrate involves a burial of hydrophobic surface and/or structural rearrangement involving substrate regions distal to the acetyl-lysine-binding site. Together, these studies suggest that substrate-specific binding by sirtuin proteins involves contributions from the zinc-binding domain of the enzyme and substrate regions distal to the acetyl-lysine-binding site.

PubMed: 15019790
DOI: 10.1016/j.jmb.2004.01.060

Experimental method

X-RAY DIFFRACTION (1.96 Å)