Figure 3.

Structural characteristics of HIV-1 activating HDACIs. Panel A: Docking of the HDACI MC2211 at the catalytic cavity of HDAC2, a class I enzyme. The different portions of the inhibitor [i.e. the CAP portion (CAP), the connection unit (CU), the hydrophobic spacer (HS), and the zinc-binding group (ZBG)] are mapped to the molecule represented in the picture. The enzyme is shown as semi-transparent Connolly surface. The Zn⁺⁺ ion embedded in the catalytic cavity is shown as a dotted sphere. The inhibitor is shown according to CPK colouring. Panels B, C: General formulas for HDACIs capable of inducing HIV-1 activation from quiescence. Panel D: Structural superimposition of the best docking poses for the HDACIs MC2113 and MC2211 within the catalytic cavity of HDAC2. Inhibitors are shown in CPK (MC2113: carbon backbone in white; MC2211: carbon backbone in cyan). The enzyme backbone is shown as cartoons. The Zn⁺⁺ ion is shown as a gray sphere. Amino acids D100, H141 and G150 (important for hydrogen bonding with the inhibitors) are shown as orange sticks.