Sulyman Barkho - Graduate Student

sbarkho (at)



Unlike macroscopic machines, flexibility and conformational changes are indispensable properties of proteins. Indeed an individual non-covalent bond is only marginally stable and changes in internal structure may be important in regulating function. I wish to explore the ability of allosteric sites to alter the relative stability of different conformations of proteins in the regulation of function. Thus, we may begin to understand the molecular and physical underpinnings that enable quantitative control of protein functionality. While this form of functional control is very important to biology, it is not well understood from either a theoretical or experimental basis. The Src family of tyrosine kinases [SFKs] are important signaling enzymes that are up-regulated in many cancers. It is important to understand how they are naturally regulated and how they use molecular cross-talk to engage large substrate proteins. Csk (C-terminal Src kinase) down-regulates SFKs by phosphorylating a single tyrosine in the C-terminus, which leads to a large conformational change that represses the catalytic activity of SFK enzymes. Thus, Csk is an inherently anti-proliferative kinase that uses a chemical reaction to induce a mechanical/dynamical motion that inhibits activity of the target enzyme. The SH2 domain of Csk was shown to be important in regulating the enzyme's activity depending on the redox state of a distal disulfide bridge. My current work focuses on understanding the intrinsic allostery and control that is observed in this system. This work could reveal interesting new dynamics in the regulatory function of Csk's SH2 domain.