Trapping a transition state in a computationally designed protein bottle

摘要: The fleeting lifetimes of the transition states (TSs) chemical reactions make determination their three-dimensional structures by diffraction methods a challenge. Here, we used packing interactions within core protein to stabilize planar TS conformation for rotation around central carbon-carbon bond biphenyl so that it could be directly observed x-ray crystallography. computational design software Rosetta was pocket threonyl-transfer RNA synthetase from thermophile Pyrococcus abyssi forms complementary van der Waals with biphenyl. This latter moiety introduced biosynthetically as side chain noncanonical amino acid p-biphenylalanine. Through iterative rounds and structural analysis, identified in which p-biphenylalanine is trapped energetically disfavored, coplanar reaction.