 | Acta Crystallographica Section F Acta Crystallographica Section F STRUCTURAL BIOLOGY COMMUNICATIONS |
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![[Figure 6]](cb5089fig6mag.jpg)
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Figure 6
One of the hinge loops of Sirt2 exhibits a high flexibility and seems to be important for inhibitor binding. (a) Superposition of the hinge loops of Sirt1, Sirt2 and Sirt3 in complex with either EX527 or CHIC35 (Sirt1, brown cartoon; Sirt2, deep salmon; Sirt3, ruby) and of the hinge loop of Sirt2–ADPR lacking an indole (dark grey). Only the hinge loop of the Sirt2–ADPR–EX243 complex adopts a different conformation, while the hinge-loop conformation of the complexes of Sirt1, Sirt2 and Sirt3 with indole is similar to that observed in the Sirt2–ADPR complex. This loop shift is induced by the binding of the hinge molecule. (b) Superposition of the Sirt2–SirReal2–NAD+ complex structure (PDB entry 4rmg; slate blue cartoon with SirReal2 in light pink sticks and NAD+ in light orange sticks) with the crystal structure of Sirt2–ADPR–EX243 (deep salmon cartoon with ADPR in yellow sticks and EX243 in light blue sticks) reveals that the hinge molecule of the Sirt2–ADPR–EX243 complex occupies the selectivity pocket that is occupied by the dimethylpyrimidine moiety (DMP) in the Sirt2–SirReal2 complex. (c) Superposition of the Sirt2–thiomyristoylated peptide complex structure (Sirt2–Thiomyr-peptide; PDB entry 4r8m; turquoise cartoon with the thiomyristoylated peptide shown as dark blue sticks) with the crystal structure of Sirt2–ADPR–EX243 shows that the hydrophobic myristoyl moiety also occupies the selectivity pocket that is occupied by the hinge molecule in the Sirt2–ADPR–EX243 complex. (d) Comparison of the conformation of the hinge loop of Sirt2 (amino acids 136–144) in the Sirt2–ADPR complex (dark grey), the Sirt2–ADPR–EX243 structure (deep salmon), the complex of Sirt2, NAD+ and SirReal2 (slate blue) and the Sirt2–thiomyristoyl peptide structure (dark turquoise). This hinge loop adopts a different conformation in all four crystal structures. Tyr139 and Pro140 of the Sirt2–thiomyristoyl peptide complex are not defined by the electron density. |
![[Figure 6]](cb5089fig6.jpg)
| STRUCTURAL BIOLOGY COMMUNICATIONS |
ISSN: 2053-230X
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