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Biochemistry Seminar – Dr. Bryan Shaw: “Measuring and manipulating the net charge of proteins – what have we been missing?””
October 16 @ 4:00 pm - 5:00 pm
Dr. Bryan Shaw
Department of Chemistry and Biochemistry
Title: “Measuring and manipulating the net charge of proteins – what have we been missing?”
Most biochemists show little interest in measuring the net electrostatic charge (Z) of folded proteins at pHpI, that is, in determining values of Z that not only account for anomalous pKa’s but also include tightly bound metal ions, cofactors, solvent or buffer ions. Our disregard for this fundamental parameter has impeded a rigorous understanding of basic biochemistry, for example, single electron transfer reactions involving metalloproteins. Opportunities in electrostatic-based medicinal chemistry have also been forgone. This seminar will discuss the first measurements of charge fluctuation during single electron transfer in metalloproteins. The results are deepening our understanding of how proteins tune the kinetic and thermodynamic properties of redox centers. The second half of this seminar will explore the idea that the Z is a “druggable” parameter that can be selectively permuted by small molecules—similar to how we use small molecules to target other classical parameters such as Vmax or Km. Here, we have designed and synthesized a set of small molecules that we refer to as “ball and chain” molecular maces. These molecules can selectively “supercharge” misfolded forms of ALS-linked superoxide dismutase-1 (SOD1) by amyloid-selective lysine acylation.
Host: Vishal Gohil
108 Biochemistry Building (Bldg.#1507)