Figure 1.
Hypothetical roles of NAD+ dependent deacetylases (sirtuin family) in the T. cruzi parasite.
Figure 2.
Sequence alignment between TcSir2rp1 and hSIRT2.
Conserved amino acids are highlighted in yellow.
Figure 3.
Molecular docking results in the productive pocket of TcSIR2rp1.
(A) Superimposition of A5dPR crystal (yellow-capped sticks) and best-ranked docking poses in hSIRT2 (green-capped sticks, cyan ribbons) and TcSIR2rp1 (white-capped sticks, dark pink ribbons). (B) NAD+ best-ranked docking pose in the TcSIR2rp1 productive form (purple-capped sticks, dark pink ribbons). (C) Nicotinamide best-ranked docking pose in the TcSIR2rp1 productive form (purple -capped sticks, dark pink ribbons). (D) AGK2 best-ranked docking pose in the TcSIR2rp1 productive form (purple-capped sticks, dark pink ribbons).
Figure 4.
Superimposition of ten NAD+ docking poses in the TcSIR2rp1 productive (A) and non-productive (B) forms.
NAD+ molecules are represented in brown-capped sticks. Protein structures are represented as ribbons and colored in dark pink and green representing the TcSIR2rp1 productive and non-productive form, respectively. Pocket surfaces were generated with MOE (MOE 2012.10; Chemical Computing Group, Montreal, Canada) and are colored in gray.
Table 1.
PLP scores for the anti-trypanosomal compounds docked into TcSIR2rp1 and TcSIR2rp3 productive forms.
Figure 5.
Molecular docking results from the virtual screening of the productive conformational state of TcSIR2rp1.
(A) Anacardic acid best-ranked docking pose in the TcSIR2rp1 productive form. (B) Aculeatin D best-ranked docking pose in the TcSIR2rp1 productive form. (C) 16-acetoxy-11-hydroxyoctadeca-17-ene-12,14-diynylethanoate best-ranked docking pose in the TcSIR2rp1 productive form. (D) Vismione D best-ranked docking pose in the TcSIR2rp1 productive form. Protein structures are represented as dark pink ribbons. Amino acids participating in protein-ligand interactions are indicated bylight gray sticks. Ligands are represented in capped sticks and are colored in orange. GRID surface are also reported in the active site pockets and are colored as yellow, blue and red to highlight the hydrophobic, electron-donor and electron-acceptor properties, respectively.