Figure 1.
Structures of the epimers quinine and quinidine.
Table 1.
Experimental IC50 values for quinidine and quinine in rat and human CYP2D taken from Venhorst et al. [1].
Table 2.
Experimental and Calculated Ki values for quinidine and quinine in both crystal structures of human CYP2D6.
Figure 2.
Sequence Alignment of Human CYP2D6 and all Rat CYP2D enzymes.
α-helices are shown in red, β-sheets in yellow and β-turns in blue. The sequence alignment was generated using both ClustalX and the MOE sequence alignment program.
Figure 3.
Ramachandran Plot for a model of rat CYP2D1 based on 2F9Q.
Figure 4.
Quinidine inducibly docked into a model of human CYP2D6 based on the 2F9Q crystal structure.
Quinidine is shown in orange inside the active site which is shown in green.
Figure 5.
Quinidine inducibly docked into a model of human CYP2D6 based on the 3QM4 crystal structure.
Quinidine is shown in orange inside the active site which is shown in green.
Figure 6.
Interaction diagram showing an overlay of quinidine (green) and quinine (orange) in a) Human 2D6 (2F9Q), b) Rat 2D2 (2F9Q), c) Human 2D6 (3QM4), d) Rat 2D2 (3QM4).
The lines shown in green are electrostatic interactions (pi bonding or H bonding).
Table 3.
Amino acid residue interactions with Quinidine and Quinine in models based on both crystal structures.
Table 4.
ΔGbinding energies calculated from docking simulations to CYP2D2 and CYP2D6 models.