Association for Cultural Diversity in Chemistry

Spring 2017 Event

Bertrand García-Moreno

Dr. García-Moreno was raised in Mexico City. Early interests in music were eclipsed by curiosity about the chemistry and physics of living systems. A youth well spent outdoors hiking and exploring the Mexican countryside further stimulated his interests in the biological world. To avoid medical school, which was then the only available pathway into biochemistry and other molecular biological sciences, but perhaps also in search of adventure and drawn by the prospect of a liberal arts education in a beautiful setting, he moved to Maine to attend Bowdoin College. In college he majored in Chemistry/Biochemistry and was able to continue to pursue his interests in music and in the outdoors. He did graduate work with Frank Gurd, one of several protein physical chemists assembled in the Department of Chemistry in Indiana University in Bloomington. A world-class music conservatory a few yards from the Department was a second home for him during his time in graduate school. His doctoral research focused on structure-based energy calculations in proteins. He completed postdoctoral training in biological thermodynamics with Gary Ackers in the Department of Biology at Johns Hopkins University and later in the Department of Biochemistry & Molecular Biophysics at Washington University School of Medicine. He returned to Hopkins in 1992 to join the faculty of the Department of Biophysics. He has chaired the Department and acted as Editor-in- Chief of the journal PROTEINS for the last decade.

Proteins as pH Sensors and Switches

Tight regulation of pH and other ionic components of the cellular milieu is the trait that is common to all living systems. Dysregulation of pH homeostasis, in turn, is the hallmark of cancer and other diseases. We are studying the roles of proteins as biological pH sensors and switches. In this lecture I will focus on our efforts to engineer protein pH sensors. Specifically, I will describe our studies of ionizable groups buried in dry or hydrophobic environments in proteins. These buried ionizable groups can have highly anomalous properties that are essential for all forms of biological energy transduction, and which can also be harnessed to engineer pH sensors and pH-driven switches. I will describe structural and energetic consequences of burial and ionization of groups buried in hydrophobic environments in proteins, consequences on the conformational landscapes, challenges to theory and simulations, and implications for the evolution and engineering of novel enzymes, pH sensors, and pH-driven switches.