Mediation of donor–acceptor distance in an enzymatic methyl transfer reaction
Abstract
During the past 30 years, the methyl transfer community has attempted to find the molecular origin of the methyltransferases’ catalytic power. This report describes a combination of experimental and computational studies of enzymatic methyl transfer catalyzed by catechol- O -methyltransferase and its mutants at position Tyr68. The results show structural and dynamical differences between WT and mutants, as well as a role for substrate ionization in the generation of active site compaction. For the first time, to our knowledge, we are able to show a trend in donor–acceptor distance in the ground state that can be correlated with catalytic efficiency. This work provides an important step forward and a clear new direction for understanding enzymatic methyl transfer.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 15, 2015
- Source ID
- 10.1073/pnas.1506792112
Entities
People
- Heather J. Kulik
- Jianyu Zhang
- Judith P. Klinman
- Todd Martinez
Organizations
- Burroughs Wellcome Fund
- California Institute for Quantitative Biosciences
- National Institutes of Health
- Stanford University
- United States Department of Defense
- Yusuf Hamied Department of Chemistry