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Structure of a ligand-binding intermediate in wild-type carbonmonoxy myoglobin

Nature volume 403, pages 921–923 (2000)Cite this article

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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Figure 1: Position of the CO molecule in states A and B.
Figure 2: Position of the CO molecule in state D.

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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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Authors and Affiliations

  1. P-21 Biophysics Group, MS-D454, Los Alamos National Laboratory, Los Alamos, 87545, New Mexico , USA

    Kelvin Chu

  2. Department of Physics, Cook Building University of Vermont, Burlington, 05405, Vermont, USA

    Kelvin Chu & Joel Berendzen

  3. Department of Biophysical Chemistry, Max Planck Institute for Molecular Physiology, Otto-Hahn-Str 11, Dortmund, 44227, Germany

    Jaroslav Vojtchovský & Ilme Schlichting

  4. Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, 87545, New Mexico, USA

    Benjamin H. McMahon

  5. Department of Biology Brookhaven National Laboratory, Upton, 11973-5000, New York, USA

    Robert M. Sweet

Authors
  1. Kelvin Chu
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  6. Ilme Schlichting
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Correspondence to Ilme Schlichting.

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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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