Babis Kalodimos, Member, St. Jude Faculty; Chair, Department of Structural Biology; St. Jude Children's Research Hospital, will give a talk on "The conformational landscape of protein kinases in physiology and disease."

Organized by Ph.D. students of the CUNY Graduate Center.

ABSTRACT

Protein kinases regulate almost every aspect of cellular function. Changes in the expression, localization in the cell, mutations or chromosomal rearrangements of kinases can cause a number of cancers and other diseases. Cancer ‘driver’ mutations occur very frequently in kinase genes. In fact, the kinase domain is the domain most frequently encoded by cancer genes. Tremendous progress has been made in understanding the structure, function, and mechanisms of regulation of protein kinases. However, it has proved challenging to monitor these transitions and structurally characterize the manifold of conformational states inherently populated by a kinase. In the absence of such information, the mechanisms underpinning the response of kinases to physiological and pathological processes remain poorly understood. I will discuss how we structurally and energetically dissect the mechanisms underpinning the function and operation of a number of important protein kinases. We elucidate regulatory and drug-resistance mechanisms as well as how key structural elements and motifs control the activation/inhibition processes in kinases.