1. A ligand-gated, hinged loop rearrangement opens a channel to a buried artificial protein cavity
- Author
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R.A. Musah, Duncan E. McRee, M.M. Fitzgerald, and David B. Goodin
- Subjects
chemistry.chemical_classification ,biology ,Cytochrome ,Protein Conformation ,Protein dynamics ,Active site ,Protonation ,Cytochrome-c Peroxidase ,Crystallography, X-Ray ,Ligands ,Biochemistry ,Small molecule ,Models, Structural ,Crystallography ,chemistry ,Structural Biology ,Oxidoreductase ,Mutagenesis, Site-Directed ,Genetics ,biology.protein ,Ligand-gated ion channel ,Binding site ,Protein Binding - 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 c peroxidase 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.
- Published
- 1996
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