Understanding How Fes and Abl Kinases Recognize Substrates and Get Activated
Author Information
Author(s): Filippakopoulos Panagis, Kofler Michael, Hantschel Oliver, Gish Gerald D., Grebien Florian, Salah Eidarus, Neudecker Philipp, Kay Lewis E., Turk Benjamin E., Superti-Furga Giulio, Pawson Tony, Knapp Stefan
Primary Institution: Structural Genomics Consortium, University of Oxford
Hypothesis
The study investigates the molecular mechanisms by which the SH2 domain of Fes and Abl kinases enhances their catalytic activity and substrate recognition.
Conclusion
The SH2 domain of Fes and Abl kinases plays a crucial role in stabilizing their active conformations and facilitating substrate recognition.
Supporting Evidence
- The SH2 domain interacts tightly with the kinase domain, stabilizing its active conformation.
- Mutations disrupting the SH2-kinase interface lead to loss of kinase activity.
- Binding of ligands to the SH2 domain enhances the stability of the kinase's active state.
- Fes and Abl kinases utilize similar mechanisms for substrate recognition and activation.
Takeaway
Fes and Abl kinases work better when their SH2 domains are active, helping them recognize and interact with their targets.
Methodology
The study involved solving the structures of the Fes SH2-kinase unit and analyzing its interactions with substrates and ligands.
Digital Object Identifier (DOI)
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