Matthew Young, Ph.D.
Assistant Professor, Biological Chemistry
Research Assistant Professor, Bioinformatics
B.A. Wesleyan University
Ph.D. Wesleyan University
Postdoctoral, University of California at Berkeley
Research Profile
Our laboratory utilizes a combination of experimental and computational approaches to study problems in protein kinases and cell signaling. Protein kinases represent one of the fundamental components of cell signal cascades that propagate signals for fundamental cellular processes including growth, differentiation, and metabolism. In higher organisms, hundreds of diverse protein kinases have evolved different molecular mechanisms to regulate the signaling states of distinct but often co-existing signaling pathways. In an example of regulation in a family of proteins we study, the Cyclin Dependent family of Kinases (CDKs), these kinases have evolved to require the binding of additional proteins, the cyclins, in order to activate their catalytic activity. Some examples of additional molecular mechanisms that have evolved to regulate catalytic activity in protein kinases include the interactions of additional domains with the catalytic core, phosphorylation-stabilized conformational transitions, the binding of external inhibitory proteins, and protein kinase localization. Our goal is to understand these regulatory mechanisms from a structural perspective, using the CDK family as a model.
From a computational approach, we employ molecular modeling approaches based upon atomic resolution chemical potential energy functions that are capable of describing detailed molecular properties of the proteins we study. Historically carried out largely on supercomputers, these simulations are now routinely carried out on clusters composed of pc-class computers linked together. Among other things, this modeling approach is used to describe the molecular motions of proteins in an in vitro environment. Coupling these models with x-ray crystallography and in vitro enzymatic assays enables us to study regulatory mechanisms from a protein dynamics, structure, and activity based perspective.
Awards
1999 Damon Runyon Cancer Research Foundation, Runyon-Winchell Fellowship
2003 - 2007 The Burroughs-Welcome Fund, “Career Award at the Scientific Interface,” postdoc/faculty transitional fellowship
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Publications
Young, M.A., S. Gonfloni, G. Superti-Furga, B. Roux, J. Kuriyan. 2001. Dynamic coupling between the SH2 and SH3 domains of c-Src and Hck underlies their inactivation by C-terminal tyrosine phosphorylation. Cell. 105, 115–126. PMID: 11301007
Nagar, B., O. Hantschel, M.A. Young, K. Scheffzek, D. Veach, W. Bornmann, B. Clarkson, G. Superti-Furga, and J. Kuriyan. 2003. Structural basis for the auto-inhibition of c-Abl tyrosine kinase, Cell, 112, 859-871. PMID: 12654251
Jeruzalmi D, Yurieva O, Zhao Y, Young M, Stewart J, Hingorani M, O'Donnell M, Kuriyan J. 2001. Mechanism of processivity clamp opening by the delta subunit wrench of the clamp loader complex of E. coli DNA polymerase III. Cell 106(4):417-28. PMID: 11525728
Arthanari, H., McConnell, K. J., Beger, R., Young, M. A., Beveridge, D. L., and Bolton, P. H. 2003. Assessment of the molecular dynamics structure of DNA in solution based on calculated and observed NMR NOESY volumes and dihedral angles from scalar coupling constants. Biopolymers 68, 3-15. PMID: 12579576
Young, M. A., B. Jayaram, and D. L. Beveridge. 1997. Intrusion of Counterions into the Spine of Hydration in the Minor Groove of B-DNA: Fractional Occupancy of Electronegative Pockets. J. Am. Chem. Soc. 119:59-69. http://pubs.acs.org/doi/abs/10.1021/ja960459m
Book Chapters
Young, M.A., and Kuriyan, J. Structures of Ser/Thr and Tyr Kinases. In Handbook of Cell Signalling. Academic Press. 2003.
