Fig. 5: Computational model of BHMeHis1.8 and its comparison to existing BH32.14 and BH32 models.
From: A non-canonical nucleophile unlocks a new mechanistic pathway in a designed enzyme
A A QM/MM model of transition state three in the reaction mechanism of BHMeHis1.8 including key active site residues, shown as atom-coloured balls and sticks (ligand shown with black carbon atoms, and active site residues with blue carbon atoms). Glu26 serves as a catalytic base for deprotonation of C2. Trp124 and Phe132 form π-stacking interactions with the electron deficient nitro-arene. Ordered water molecules are shown as balls and sticks. B DFT model of transition state 3 in the reaction mechanism of BH32.1413 including active site residues shown in atom-coloured balls and sticks (ligand shown with black carbon atoms, and active site residues with grey carbon atoms). Arg124 is shown to stabilize oxyanion intermediates throughout the mechanism. Proton transfer is mediated by an ordered water molecule. C Computational design model for BH3229. A composite transition state model and surrounding key residues are shown in atom-coloured balls and sticks (ligand shown with black carbon atoms, and active site residues with white carbon atoms). Gln128 was designed to stabilize C1 oxyanion. An ordered water molecule (shown as a red sphere) was designed to stabilize the C3 oxyanion and to mediate proton transfer.
