title: A ligand-gated, hinged loop rearrangement opens a channel to a buried artificial protein cavity.
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.
authors.affiliation: Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Fitzgerald
authors.forename: R A
authors.initials: RA
authors.lastname: Musah
authors.forename: D E
authors.initials: DE
authors.lastname: McRee
authors.forename: D B
authors.initials: DB
authors.lastname: Goodin
mesh_terms: D018360:Crystallography, X-Ray; D003578:Cytochrome-c Peroxidase / Q000737:chemistry*; D008024:Ligands; D008961:Models, Structural; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D008024:Ligands; D003578:Cytochrome-c Peroxidase