These authors contributed equally.
Efforts Toward the Direct Experimental Characterization of Enzyme Microenvironments: Tyrosine100 in Dihydrofolate Reductase†
Article first published online: 3 APR 2009
Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 48, Issue 19, pages 3478–3481, April 27, 2009
How to Cite
Groff, D., Thielges, Megan C., Cellitti, S., Schultz, Peter G. and Romesberg, Floyd E. (2009), Efforts Toward the Direct Experimental Characterization of Enzyme Microenvironments: Tyrosine100 in Dihydrofolate Reductase. Angew. Chem. Int. Ed., 48: 3478–3481. doi: 10.1002/anie.200806239
This work was supported by the National Science Foundation (MCB 0346967 to F.E.R); any opinions, findings, and conclusions expressed here are those of the authors and do not necessarily reflect the views of the National Science Foundation. This work was also supported by the National Institutes of Health (PN2 EY01824 and R01 GM062159 to P.G.S.).
- Issue published online: 23 APR 2009
- Article first published online: 3 APR 2009
- Manuscript Received: 20 DEC 2008
- National Science Foundation. Grant Number: 0346967
- National Institutes of Health. Grant Numbers: PN2 EY01824, R01 GM062159
- dihydrofolate reductase;
- enzyme catalysis;
- IR spectroscopy;
- noncovalent interactions
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 occuring 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.