Affiliation:
1. Department of Biochemistry, Beckman Center, Stanford University, Stanford, United States
2. Molecular and Cellular Biochemistry Department, Indiana University Bloomington, Bloomington, United States
Abstract
Enzymes enable life by accelerating reaction rates to biological timescales. Conventional studies have focused on identifying the residues that have a direct involvement in an enzymatic reaction, but these so-called ‘catalytic residues’ are embedded in extensive interaction networks. Although fundamental to our understanding of enzyme function, evolution, and engineering, the properties of these networks have yet to be quantitatively and systematically explored. We dissected an interaction network of five residues in the active site of Escherichia coli alkaline phosphatase. Analysis of the complex catalytic interdependence of specific residues identified three energetically independent but structurally interconnected functional units with distinct modes of cooperativity. From an evolutionary perspective, this network is orders of magnitude more probable to arise than a fully cooperative network. From a functional perspective, new catalytic insights emerge. Further, such comprehensive energetic characterization will be necessary to benchmark the algorithms required to rationally engineer highly efficient enzymes.
Funder
National Institutes of Health (NIH)
U.S. Department of Energy
National Center for Research Resources (NCRR)
National Institute of General Medical Sciences (NIGMS)
Biomedical Technology Program
National Science Foundation (NSF)
Max-Planck-Gesellschaft
Publisher
eLife Sciences Publications, Ltd
Subject
General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience
Cited by
59 articles.
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