Combining inorganic, biophysical and structural chemistry, Professor Keith Hodgson investigates how structure at molecular and macromolecular levels relates to function. Studies in the Hodgson lab have pioneered the use of synchrotron x-radiation to probe the electronic and structural environment of biomolecules. Recent efforts focus on the applications of x-ray diffraction, scattering and absorption spectroscopy to examine metalloproteins that are important in Earth’s biosphere, such as those that convert nitrogen to ammonia or methane to methanol.
Keith O. Hodgson was born in Virginia in 1947. He studied chemistry at the University of Virginia (B.S. 1969) and University of California, Berkeley (Ph.D. 1972), with a postdoctoral year at the ETH in Zurich. He joined the Stanford Chemistry Department faculty in 1973, starting up a program of fundamental research into the use of x-rays to study chemical and biological structure that made use of the unique capabilities of the Stanford Synchrotron Radiation Lightsource (SSRL). His lab carried out pioneering x-ray absorption and x-ray crystallographic studies of proteins, laying the foundation for a new field now in broad use worldwide. In the early eighties, he began development of one of the world's first synchrotron-based structural molecular biology research and user programs, centered at SSRL. He served as SSRL Director from 1998 to 2005, and SLAC National Accelerator Laboratory (SLAC) Deputy Director (2005-2007) and Associate Laboratory Director for Photon Science (2007-2011).
Today the Hodgson research group investigates how molecular structure at different organizational levels relates to biological and chemical function, using a variety of x-ray absorption, diffraction and scattering techniques. Typical of these molecular structural studies are investigations of metal ions as active sites of biomolecules. His research group develops and utilizes techniques such as x-ray absorption and emission spectroscopy (XAS and XES) to study the electronic and metrical details of a given metal ion in the biomolecule under a variety of natural conditions.
A major area of focus over many years, the active site of the enzyme nitrogenase is responsible for conversion of atmospheric di-nitrogen to ammonia. Using XAS studies at the S, Fe and Mo edge, the Hodgson group has worked to understand the electronic structure as a function of redox in this cluster. They have developed new methods to study long distances in the cluster within and outside the protein. Studies are ongoing to learn how this cluster functions during catalysis and interacts with substrates and inhibitors. Other components of the protein are also under active study.
Additional projects include the study of iron in dioxygen activation and oxidation within the binuclear iron-containing enzyme methane monooxygenase and in cytochrome oxidase. Lab members are also investigating the role of copper in electron transport and in dioxygen activation. Other studies include the electronic structure of iron-sulfur clusters in models and enzymes.
The research group is also focusing on using the next generation of x-ray light sources, the free electron laser. Such a light source, called the LCLS, is also located at SLAC. They are also developing new approaches using x-ray free electron laser radiation to image noncrystalline biomolecules and study chemical reactivity on ultrafast time scales.
Chapman, H. N., Barty, A., Bogan, M. J., Boutet, S., Frank, M., & Hajdu, J. (2006). Femtosecond diffractive imaging with a soft-X-ray free-electron laser. NATURE PHYSICS, 2(12), 839-843.
Cohen, A. E., Soltis, S. M., Gonzalez, A., Aguila, L., Alonso-Mori, R., Barnes, C. O., … Hodgson, K. O. (2014). Goniometer-based femtosecond crystallography with X-ray free electron lasers. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(48), 17122–17127.
Kroll, T., Hadt, R. G., Wilson, S. A., Lundberg, M., Yan, J. J., & Solomon, E. I. (2014). Resonant Inelastic X-ray Scattering on Ferrous and Ferric Bis-imidazole Porphyrin and Cytochrome c: Nature and Role of the Axial Methionine-Fe Bond. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 136(52), 18087-18099.
Dey, A., Jenney, F. E., Adams, M. Ww., Babini, E., Takahashi, Y., & Solomon, E. I. (2007). Solvent tuning of electrochemical potentials in the active sites of HiPIP versus ferredoxin. SCIENCE, 318(5855), 1464-1468.
Kjaergaard, C. H., Qayyum, M. F., Wong, S. D., Xu, F., Hemsworth, G. R., & Solomon, E. I. (2014). Spectroscopic and computational insight into the activation of O2 by the mononuclear Cu center in polysaccharide monooxygenases. Proceedings of the National Academy of Sciences of the United States of America, 111(24), 8797-8802.
Lesley, S. A., Kuhn, P., Godzik, A., Deacon, A. M., Mathews, I., & Stevens, R. C. (2002). Structural genomics of the Thermotoga maritima proteome implemented in a high-throughput structure determination pipeline. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 99(18), 11664-11669.
Cho, J., Jeon, S., Wilson, S. A., Liu, L. V., Kang, E. A., & Nam, W. (2011). Structure and reactivity of a mononuclear non-haem iron(III)-peroxo complex. NATURE, 478(7370), 502-505.
Ha, Y., Tenderholt, A. L., Holm, R. H., Hedman, B., Hodgson, K. O., & Solomon, E. I. (2014). Sulfur K-Edge X-ray Absorption Spectroscopy and Density Functional Theory Calculations on Monooxo Mo-IV and Bisoxo Mo-VI Bis-dithiolenes: Insights into the Mechanism of Oxo Transfer in Sulfite Oxidase and Its Relation to the Mechanism of DMSO Reductase. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 136(25), 9094-9105.
Sarangi, R., George, S. Db., Rudd, D. J., Szilagyi, R. K., Ribas, X., & Solomon, E. I. (2007). Sulfur K-edge X-ray absorption spectroscopy as a probe of ligand-metal bond covalency: Metal vs ligand oxidation in copper and nickel dithiolene complexes. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 129(8), 2316-2326.