Gosset Molecular Classification
Protein Domain, Allosteric regulatory site
Other Names
Myristoyl-binding pocket of ABL1, Myristate-binding pocket of ABL1
Disease Roles
ABL1 Myristoyl Pocket Overview
The ABL1 myristoyl pocket is a deep hydrophobic cavity located in the C-lobe of the kinase domain of the ABL1 protein. It plays a crucial regulatory role by binding to either an N-terminal myristoyl group or small-molecule inhibitors, which induces conformational changes and stabilizes an autoinhibited state, reducing kinase activity. Targeting this site offers therapeutic potential for overcoming resistance seen with traditional ATP-site tyrosine kinase inhibitors.
Mechanism of Action
Allosteric inhibition; stabilizes inactive ABL1 conformation
Biological Functions
Allosteric regulation
Autoinhibition maintenance
Protein-protein interaction regulation
Disease Associations
Cancer
Chronic Myeloid Leukemia
Drug resistance
Safety Considerations
- Potential for off-target effects due to structural similarity with other proteins.
- Development of resistance to allosteric inhibitors.
Interacting Drugs
Asciminib (ABL001)