个人简介

BS 1993, University of California, San Diego PhD 1998, University of California, San Diego NIH Postdoctoral Fellow 1998-2002, University of California, Berkeley

研究领域

Enzymology and Bio-Inorganic Chemistry/Enzymology and Electronic Structure of Non-heme Fe/Hydrogen Tunneling Effects in Biological C-H Activation/Biomimetic Nanocluster Self-Assembly

Biological responses to O2 are highly complex, and rely on specific enzyme action. I am interested in understanding how biology controls the metal cofactors and protein recognition involved in O2-sensing, discovering bio-mimetic systems for controlled oxidation chemistry, and developing fluorescence-based sensors. Cellular responses to O2 are key factors in human health and disease. My group is combining the tools of enzymology and chemistry to understand the reactivity, dynamics, and regulation of human enzymes that sense O2 through their action on the transcription factor called the hypoxia inducible factor (HIF). These enzymes are Fe(II), alpha-ketuglutarate dependent oxygenases called HIF-hydroxylases, which turn-off HIF in the presence of O2. The long-range goal of this work is to discover how the HIF-hydroxylases are regulated, understand the catalysis of O2-activation, and understand how these enzymes recognize and bind the conformationally flexible HIF substrate. Hybrid nanoparticle/protein adducts are fantastic models for protein-protein interactions, and hold great promise for engineered materials, but a key limitation has been to relate protein structure to function in the hybrid materials. My group is applying biophysical and kinetics tools to understand the structure and reactivity of oxidation enzymes which are non-covalently bound to nanomaterials. Our work shows that substrate selectivity can be greatly altered, even while retaining native protein and cofactor structure. Another area of investigation is the role of low-amplitude protein conformational changes and dynamics on reactivity and macromolecular recognition. Through our work on such bio-mimetic systems, we hope to uncover new views of how proteins recognize, and react with, other large bio-macromolecules. Explosives sensing is of incredible importance for modern shipping and law enforcement. We work with a simple family of fluorescent coordination complexes which are useful in new explosives-sensing strategies, as well as serving as a great model to understand photoinduced transfer. We have discovered a sensor-array format for discriminating different explosives molecules, as well as a turn-on fluroscence sensor for explosives. Current directions are to relate structure to photochemical reactivity in this exciting family of coordination complex, both for improved sensing as well as to explore further applications of photo-induced charge transfer.

近期论文

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Taabazuing, C. Y.; Hangasky, J.A.; Knapp, M. J. "Oxygen Sensing Strategies in Mammals and Bacteria, " J. Inorg. Biochem., (accepted) Light, K. M.; Hangasky, J.A.; Knapp, M. J.; Solomon, E. I. "First- and second-sphere contributions to Fe(II) site activation by cosubstrate binding in non-heme Fe enzymes, " Dalton Trans., Volume 43, 2014, 1505-1508 Light, K. M.; Hangasky, J. A.; Knapp, M. J.; Solomon, E. I. "Spectroscopic Studies of the Mononuclear Nonheme Fell Enzyme FIH: Second-Sphere Contributions to Reactivity," J. Amer. Chem. Soc., Volume 135, 2013, 9665-9674 Pektas, S.; Knapp, M. J.; "Substrate preference of the HIF-prolyl hydroxylase-2 (PHD2) and substrate-induced conformational change, " J. Inorg. Biochem., Volume 126, 2013, 55-60