Welcome to the Roth Group

Dr. Justine P. Roth       Associate Professor Phone: 410-516-7835 Office: 121 Remsen Email: jproth@jhu.edu Assistant Professor:         Johns Hopkins University,    2003-2009 Dreyfus Teacher-Scholar (2008), Sloan Fellow (2007), Reseach Corp. Cottrell Scholar (2006), NSF CAREER (2005) NIH Postdoctoral Fellow:         U. California, Berkeley        2000-2003        PhD: U. Washington, Seattle  1995-2000

BIOINORGANIC & BIOPHYSICAL CHEMISTRY

The Roth group pursues problems at the interface of biological, inorganic and physical chemistry especially those related to oxidative processes within proteins. 

Biological Proton-Coupled Electron Transfer: In certain enzymes, metal ions mediate the coupled transfer of electrons and protons.  The transformations, referred to as proton-coupled electron transfer (PCET), can be highly selective occurring site-specifcally and forming radicals derived from amino acid side chains.  These protein radicals catalyze reactions central to a variety of physiological functions, from the biosynthesis of prostanoids to the transduction of light to chemical energy during photosynthesis.  [In contrast, amino acid radicals produced in uncontrolled reactions lead to pathophysiological events such as protein damage and enzyme deactivation.]  We are pursuing the hypothesis that concerted PCET is required for catalytic amino acid radical formation.  By investigating related proteins, we are asking how conserved elements of structure facilitate certain mechanisms.  We are also investigating the quantum mechanical features which allow PCET to occur over large distances more typical of electron transfer. 

Oxygen Isotope Effects: The interaction of molecular oxygen and hydrogen peroxide with metals (e.g. Cu, Fe and Mn) is a primary step in life-sustaining oxidative events. A portion of our research is dedicated to exploring metal-activated oxygen species. Because of their transient natures, these intermediates  are often undetected by spectroscopy and difficult to identify using conventional mechanistic approaches.  We are, therefore, developing new isotopic probes for studying discreet oxygen activation events.  This research encompasses the experimental and computational determination of oxygen isotope effects from molecular vibrational frequencies. Analyzing changes in oxygen isotope distributions in the context of the appropriate theory allows us to deduce structures of reactive intermediates which would otherwise escape detection. 

Principles of Redox Catalysis: An important objective of our studies is to understand the strategies used by enzymes to catalyze difficult chemical transformations, such that they occur selectively and at rates which are accelerated relative to the un-catalyzed reaction.  To this end, we compare reactions in proteins to those which occur by the same mechanism in solution, under carefully controlled conditions.  Through the application of theory we evaluate the importance of intrinsic and thermodynamic factors in determining reaction rates.  This approach allows us to also assess the probability of quantum mechanical events which can manifest in the active site differently than in solution.