 | Acta Crystallographica Section F Acta Crystallographica Section F STRUCTURAL BIOLOGY COMMUNICATIONS |
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![[Figure 5]](cb5089fig5mag.jpg)
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Figure 5
The indole inhibitors CHIC35 and EX243 interact with the residues of the active site of Sirt2 in a similar fashion as observed in other sirtuin–indole complexes. (a) The residues that interact with the two molecules of CHIC35 (a) or EX243 (c) are shown as sticks. Asn168 and Ile169, which are located beneath the ECS molecules, are not labelled. Pro94, Phe96, Leu103, Phe119, Leu134 and Leu138 are not shown for the sake of clarity. The carboxamide moiety of the ECS molecule of both Sirt2–ADPR–indole complexes hydrogen-bonds to the highly conserved residues Asp170 and Ile169 and, via a structural water, to Ala85, Ile93 and Pro94 (not shown). For both inhibitors, the amide of the ECS molecule interacts with Gln169 and, via another structural water, with ADPR and Asn168. The aromatic chlorinated indole protrudes into the hydrophobic extended C-site. The binding of the hinge molecule is mainly driven by hydrophobic interactions with the side chains of Leu103, Phe119, Phe131, Ala135, Leu138 (not shown), Tyr139 and Phe190. Additionally, the carboxamide moiety of the hinge molecule also hydrogen-bonds to the backbone carbonyl O atom of Leu138 (not shown), Tyr139, Gly141 and, via a structural water, to Asp170. Waters are shown as yellow spheres and hydrogen bonds are shown as grey dashes. (b, d) The binding mode of the ECS molecule of both Sirt2–ADPR–indole complexes is very similar to that observed in the analogous complexes of Sirt1 (brown, PDB entry 4i5i) or Sirt3 (ruby, PDB entry 4bvb). |
![[Figure 5]](cb5089fig5.jpg)
| STRUCTURAL BIOLOGY COMMUNICATIONS |
ISSN: 2053-230X
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