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A ligand-gated, hinged loop rearrangement opens a channel to a buried artificial protein cavity

Nature Structural Biology volume 3, pages 626–631 (1996)Cite this article

Abstract

Conformational changes that gate the access of substrates or ligands to an active site are important features of enzyme function. In this report, we describe an unusual example of a structural rearrangement near a buried artificial cavity in cytochrome cperoxidase that occurs on binding protonated benzimidazole. A hinged main-chain rotation at two residues (Pro 190 and Asn 195) results in a surface loop rearrangement that opens a large solvent-accessible channel for the entry of ligands to an otherwise inaccessible binding site. The trapping of this alternate conformational state provides a unique view of the extent to which protein dynamics can allow small molecule penetration into buried protein cavities.

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Authors and Affiliations

  1. Department of Molecular Biology, MB8, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, California, 92037, USA

    Melissa M. Fitzgerald, Rabi A. Musah, Duncan E. McRee & David B. Goodin

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  1. Melissa M. Fitzgerald
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  2. Rabi A. Musah
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  3. Duncan E. McRee
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  4. David B. Goodin
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Fitzgerald, M., Musah, R., McRee, D. et al. A ligand-gated, hinged loop rearrangement opens a channel to a buried artificial protein cavity. Nat Struct Mol Biol 3, 626–631 (1996). https://doi.org/10.1038/nsb0796-626

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