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Akif Tezcan
Bioinorganic and biophysical chemistry: Metalloprotein structure, function and biosynthesis.
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| Contact Information |
| Office: UH 6218 |
| Phone: (858) 534-4862 |
| Fax: (858) 534-6157 |
| Email: tezcan@ucsd.edu |
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| View group members
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| Education and Appointments |
| 2001 |
Ph.D., California Institute of Technology
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| 1995 |
B.A., Macalester College
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| Awards and Academic Honors |
| 2008 |
Beckman Young Investigator Award |
| 2007 |
NSF CAREER Award |
| 2005 |
Chris and Warren Hellman Faculty Scholar |
| 2001-2005 |
Burroughs-Wellcome and Helen Hay Whitney Postdoctoral Fellow, California Institute of Technology |
| 2001 |
Herbert Newby McKoy Award for Graduate Research |
| Research Interests |
The projects in the Tezcan group focus on the elucidation of metal-catalyzed biological redox reactions, and the control of biological processes through coordination chemistry.
Understanding Biological Nitrogen Fixation
There are few reactions in nature that can simultaneously match the global importance, socioeconomic impact, biological complexity and chemical challenge of nitrogen fixation. The conversion of molecular nitrogen (N2) into bioavailable forms such as ammonia (NH3) is essential for the biosynthesis of amino and nucleic acids, as well as the production of fertilizers and countless industrial chemicals. The extreme conditions required by the industrial nitrogen fixation processes, however, translate into an immense dependence on fossil fuels and account for >1% of all human energy consumption. This energy demand, coupled with dwindling fuel supplies and rapid rise in greenhouse gas emissions, makes it an absolute necessity to seek clean and efficient means for NH3 production. Our goal towards this end is to elucidate the molecular mechanism of nitrogenase, a redox-metalloenzyme that catalyzes N2-fixation at ambient conditions.
What sets nitrogenase apart from most biological redox systems is its requirement of 16 ATP molecules for a single catalytic turnover reaction despite a favorable driving force. In separate but connected projects, we aim 1) to understand why and how ATP-hydrolysis is involved in nitrogen fixation, and 2) to drive the nitrogenase reaction by using light or electrochemical energy instead of ATP hydrolysis in order to achieve a better control and understanding of N2-activation. Tackling this complex system requires a multi-disciplinary effort. Towards this end, we utilize a diverse array of tools, ranging from chemical synthesis, molecular biology and anaerobic protein biochemistry to X-ray crystallography, fluorescence spectroscopy, electrochemistry and photochemistry.
Metal-Mediated Protein-Protein Interactions
Protein-protein interactions (PPI's), whether formed transiently during signal transduction or permanently in macromolecular assemblies like ribosomes and RNA polymerases, are central to all cellular processes. The goal of this project is to develop tools based on inorganic coordination chemistry to guide protein-protein docking interactions, and apply them towards 1) the rational assembly of protein supramolecular structures and lattices, and 2) the control of biological reactions and signaling pathways.
Protein-protein docking interactions are guided by the superposition of many weak forces spread over large surfaces, making the control and design of PPI's a tremendous challenge. In contrast to the forces that typically mediate PPI's, metal-ligand interactions are strong, highly directional and, in most cases, under thermodynamic control. We are using a combination of site-directed mutagenesis, chemical synthesis and unnatural amino-acid incorporation to create stable metal-coordination sites on protein surfaces that provide building blocks for metal-mediated assembly of protein superstructures.
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| Primary Research Area: |
Interdisciplinary Specialties: |
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Inorganic Chemistry
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Biophysics
Macromolecular Structure
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| Selected Publications |
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"The Nitrogenase MoFe-Protein at 1.16 Å Resolution: A Central Ligand in the MoFe-cofactor" With O. Einsle, S. L. A. Andrade, B. Schmid, M. Yoshida, J. B. Howard, D. C. Rees. Science, 297, 1696-1700 (2002).
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"Nitrogenase Complexes: Multiple Docking Sites for a Nucleotide Switch Protein" With J. T. Kaiser, D. Mustafi, M. Y. Walton, J. B. Howard, D. C. Rees. Science, 309, 1377-1380 (2005).
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"Controlling Protein-Protein Interactions through Metal Coordination: Assembly of a 16-Helix Bundle Protein" With E. N. Salgado and J. Faraone-Mennella, J. Am. Chem. Soc., 129, 13374-13375 (2007).
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"Metal-Mediated Self-Assembly of Protein Superstructures: Influence of Secondary Interactions on Protein Oligomerization and Aggregation" With E. N. Salgado, R. A. Lewis and J. Faraone-Mennella, J. Am. Chem. Soc., 130, 6082-6084 (2008).
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Control of Protein Oligomerization Symmetry by Metal Coordination. C2 and C3 Symmetrical Assemblies through Cu(II) and Ni(II) Coordination With E. N. Salgado, R. A. Lewis, S. Mossin, A. L. Rheingold, Inorg. Chem., 48, 2726-2728 (2009)
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A Superprotein Triangle Driven by Nickel(II) Coordination: Exploiting Non-Natural Metal Ligands in Protein Self-Assembly With R. J. Radford, J. Am. Chem. Soc., 131, 9136-9137 (2009).
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