Fig. 5: Bortezomib binding promotes hClpXP to adopt a proteolytically active conformation.
From: Cryo-EM structures of human ClpXP reveal mechanisms of assembly and proteolytic activation
a Atomic models of the compact hClpX-bound hClpP and b the extended bortezomib-bound hClpP tetradecamers are shown as secondary structure cartoons, with insets highlighting the active site conformations represented as ribbons with salient residues as sticks. To determine our hClpX-bound hClpP structure, S153 was mutated to alanine, but is shown in (a) as a serine for visualization purposes. In the proteolytically inactive conformation, the imidazole of H178 is positioned too far from S153 for peptide hydrolysis. Conversely, in the bortezomib-bound hClpP, the active site adopts a proteolytically active conformation, with H178 shifting towards S153 in proximity for catalysis.
