Extended Data Fig. 6: Discrimination of enantiomeric transition states by DA7.
From: Efficient Lewis acid catalysis of an abiological reaction in a de novo protein scaffold
a, Whereas the equilibrated rate-limiting transition state leading to the experimentally observed (4R, 6R)-hetero-Diels-Alder product binds productively at the DA7 active site (TS1-endo, green; see also Fig. 3 in the main text), severe steric clashes between the indole moiety of the enantiomeric TS1-endo (yellow sticks) and the protein backbone are observed if the azachalcone moiety chelates the catalytic zinc ion. b, Restrained molecular dynamics simulations show that the clashes between the enantiomeric TS1-endo and DA7 are only relieved at the expense of zinc coordination, explaining why the evolved enzyme does not produce the (4S, 6S)-hetero-Diels-Alder product. Labelled distances are in angstrom. c, d, Surface representation of DA7 showing the binding pocket with the preferred transition state docked at the active site in stick (c) and space-filling (d) representation.
