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Cupin Variants as a Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes
Author(s) -
Fujieda Nobutaka,
Ichihashi Haruna,
Yuasa Miho,
Nishikawa Yosuke,
Kurisu Genji,
Itoh Shinobu
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202000129
Subject(s) - stereoselectivity , chemistry , michael reaction , stereochemistry , ligand (biochemistry) , macromolecule , enantioselective synthesis , ketone , docking (animal) , combinatorial chemistry , catalysis , organic chemistry , biochemistry , receptor , medicine , nursing
Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double‐stranded β‐barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo‐ and enantioselective Michael addition reaction of nitroalkanes to an α,β‐unsaturated ketone. Moreover, calculated substrate docking signified C106N and F104W single‐point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.