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Updated: Jun 30, 2026

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR
Published on: December 16, 2013
The biochemical architecture of an ancient adaptive landscape
Mark Lunzer1, Stephen P Miller, Roderick Felsheim
1BioTechnology Institute, Evolution and Behavior, University of Minnesota, St. Paul, MN 55108, USA.
Abstract:
Molecular evolution is moving from statistical descriptions of adaptive molecular changes toward predicting the fitness effects of mutations. Here, we characterize the fitness landscape of the six amino acids controlling coenzyme use in isopropylmalate dehydrogenase (IMDH). Although all natural IMDHs use nicotinamide adenine dinucleotide (NAD) as a coenzyme, they can be engineered to use nicotinamide adenine dinucleotide phosphate (NADP) instead. Intermediates between these two phenotypic extremes show that each amino acid contributes additively to enzyme function, with epistatic contributions confined to fitness. The genotype-phenotype-fitness map shows that NAD use is a global optimum.
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