Abstract
Small molecules such as NO, O2, CO or H2 are important biological ligands that bind to metalloproteins to function crucially in processes such as signal transduction, respiration and catalysis. A key issue for understanding the regulation of reaction mechanisms in these systems is whether ligands gain access to the binding sites through specific channels and docking sites, or by random diffusion through the protein matrix. A model system for studying this issue is myoglobin, a simple haem protein. Myoglobin has been studied extensively by spectroscopy, crystallography, computation and theory1,2,3,4,5,6,7,8,9,10,11. It serves as an aid to oxygen diffusion but also binds carbon monoxide, a byproduct of endogenous haem catabolism. Molecular dynamics simulations3,4,5, random mutagenesis6 and flash photolysis studies7,8,9,10 indicate that ligand migration occurs through a limited number of pathways involving docking sites. Here we report the 1.4 Å resolution crystal structure of a ligand-binding intermediate in carbonmonoxy myoglobin that may have far-reaching implications for understanding the dynamics of ligand binding and catalysis.
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Acknowledgements
The work was generously supported by the Human Frontiers Science Program (to I.S. and J.B.), the Bundesministerium für Bildung und Forschung (to I.S.) and the Richard and Anne-Liese Gielen-Leyendecker-Stiftung (to I.S.). Beamline X12C is supported by the US Department of Energy Offices of Health and Environmental Research and of Basic Energy Sciences, and by the National Science Foundation. We are grateful to H. Frauenfelder for stimulating discussions, G. Holtermann for expert technical assistance, and R. S. Goody for continuous support and encouragement.
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Chu, K., Vojtchovský, J., McMahon, B. et al. Structure of a ligand-binding intermediate in wild-type carbonmonoxy myoglobin. Nature 403, 921–923 (2000). https://doi.org/10.1038/35002641
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DOI: https://doi.org/10.1038/35002641
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