Year: 2009
Type: article
Abstract: We should have said, reversible inhibitor. That is the key to the use of active-site-directed ligands as pharmacological chaperones. An inhibitor that binds irreversibly to a target protein takes that protein out of circulation, activity-wise. But a reversible inhibitor always allows the presence of some equilibrium amount of free enzyme [12], which is then available for substrate binding (which will also stabilize the protein). The affinity of the inhibitor is also important. If it binds too tightly, it may be effectively irreversible. But if it binds too weakly, it may impossible to supply a high enough concentration of the chaperone to be effective. In practice, inhibitors with a Ki (equilibrium disassociation constant) close to the Km (Michaelis-Menten constant) of the substrate or a bit tighter seem to be useful.
Source: Journal of Biology
DOI: 10.1186/jbiol186
Authors: Dagmar Ringe, Gregory A Petsko
Institution: Brandeis University
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,686
OpenAlex ID: W2118098299