1s5p
From Proteopedia
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Structure and substrate binding properties of cobB, a Sir2 homolog protein deacetylase from Eschericia coli.
Overview
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.
About this Structure
1S5P is a Single protein structure of sequence from Escherichia coli with ZN as ligand. Full crystallographic information is available from OCA.
Reference
Structure and substrate binding properties of cobB, a Sir2 homolog protein deacetylase from Escherichia coli., Zhao K, Chai X, Marmorstein R, J Mol Biol. 2004 Mar 26;337(3):731-41. PMID:15019790
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