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Figure 1.
Figure 1. Structure of the Ternary Complex of Sir2Tm Bound
to Acetylated Peptide and NAD^+
(A) Overall structure of
Sir2Tm bound to an acetylated peptide corresponding to residues
372–389 of the p53 protein (yellow) and β-NAD^+ (gray). The
Sir2Tm Rossmann fold domain, the α-helical subdomain and Zn
binding subdomain, and the Zn atom are colored teal, blue, and
gold, respectively.
(B) Electron density for the sirtuin
substrates. The 2F[o] − F[c] electron density map contoured at
1σ is shown surrounding the acetylated p53 peptide (yellow) and
β-NAD^+ bound to the active site of Sir2Tm.
(C)
Stereodiagram of NAD^+ (white) in the active site of Sir2Tm
(teal) bound to acetylated peptide (yellow). Active site
residues that make contact with NAD^+ are shown as lines, the
acetyl lysine substrate and NAD^+ are shown as sticks, and water
contacts are shown as dashed, gray sticks.
(D) Schematic
representation of Sir2Tm contacts with NAD^+ and acetyl lysine.
Sir2Tm residues are shown as ovals containing the amino acid
designation and number; invariant residues shaded in blue,
waters are shown as red circles, and the acetyl lysine side
chain is designated as Ac-K and shaded yellow. Hydrogen bonds
between NAD^+ and backbone amides and carbonyls are shown as
blue and red dashes, respectively. Hydrogen bonds to amino acid
side chains are represented as green dashes, and van der Waals
interactions are indicated by yellow semicircles.
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