Groff Dan, Thielges Megan C, Cellitti Susan, Schultz Peter G, Romesberg Floyd E
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Angew Chem Int Ed Engl. 2009;48(19):3478-81. doi: 10.1002/anie.200806239.
State secrets: Site-specific deuteration and FTIR studies reveal that Tyr100 in dihydrofolate reductase plays an important role in catalysis, with a strong electrostatic coupling occurring between Tyr100 and the charge that develops in the hydride-transfer transition state (see picture, NADP(+) purple, Tyr100 green). However, relaying correlated motions that facilitate catalysis from distal sites of the protein to the hydride donor may also be involved.