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Discovery of new ligand binding pathways in myoglobin by random mutagenesis

Abstract

A random library of single amino acid mutants of myoglobin was generated using a highly efficient, single–base–misincorporation random mutagenesis method to discover new ligand–binding pathways in myoglobin. A surprisingly large fraction of the library exhibits ligand–binding kinetics that are substantially different from the wild–type protein. In addition to residues 45, 64 and 68, which comprise the best studied ligand–binding pathway single mutations of several other clusters of residues far away from that pathway are discovered which profoundly affect the ligand–binding kinetics. These results provide a new approach to explore the relationship between the fluctuations in protein structure and function.

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Huang, X., Boxer, S. Discovery of new ligand binding pathways in myoglobin by random mutagenesis. Nat Struct Mol Biol 1, 226–229 (1994). https://doi.org/10.1038/nsb0494-226

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  • DOI: https://doi.org/10.1038/nsb0494-226

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