Mechanism of Action of Cyclophilin A Explored by Metadynamics Simulations
Figure 6
Proposed mechanism of action for CypA.
CypA sequesters the most abundant conformation in water, trans0, that is rapidly interconverted into the most abundant conformer trans180. Then, CypA catalyzes the isomerization of the peptide along TS2, producing the mostly populated minimum, cis180. The peptide most probably detaches in the cis180 conformation. This readily interconverts to cis0 once the peptide is in aqueous solution. CypA residues that form important H-bonds (hhb) and hydrophobic interactions (nnb) with the G3P4 moiety are shown. Residues with almost exclusive relevance to each conformation are highlighted in red.