A LIGAND-GATED, HINGED LOOP REARRANGEMENT OPENS A CHANNEL TO A BURIEDARTIFICIAL PROTEIN CAVITY

Conformational changes that gate the access of substrates or ligands t o an active site are important features of enzyme function. In this re port, we describe an unusual example of a structural rearrangement nea r 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 rearrangemen t that opens a large solvent-accessible channel for the entry of ligan ds to an otherwise inaccessible binding site. The trapping of this alt ernate conformational state provides a unique view of the extent to wh ich protein dynamics can allow small molecule penetration into buried protein cavities.