Charles T Lauhon, PhD
Our major research interest is the biochemistry of tRNA modification. Protein enzymes that modify individual bases of tRNA are especially interesting because their substrates are single nucleotides within a large highly structured tRNA molecule. Thus, these enzymes are able to recognize not only the nucleotide to be modified but also the surrounding RNA structure. Although many tRNA base modifications are simple chemically, many are crucial for maintaining fidelity during translation and the enzymes required for their biosynthesis often display unique reaction mechanisms. In addition, some modifications in bacteria are required for viabliity and are thus potential antibiotic targets. We are interested in studying the mechanistic enzymology of these transformations through the use of organic chemistry (synthesis of alternate substrates and inhibitors), enzymology (establishing a chemical and kinetic mechanism) and molecular biology (to probe RNA substrate specificity). Current focus is on the development of rational design strategies for the discovery of antibiotics that target tRNA modification enzymes in bacteria.
Background: Chuck received his BS degree in chemistry (1986) from the Massachusetts Institute of Technology and a PhD degree in chemistry (1992) from the University of California-Berkeley. He was a Damon Runyon-Walter Winchell Cancer Research Fellow in the Department of Molecular Biology at the Massachusetts General Hospital. He joined the School of Pharmacy faculty in the fall of 1996. His research interests are in the biochemistry of tRNA modification and nucleic acid chemistry.
Professional Interests: RNA biochemistry and medicinal chemistry
- BS 1986 Chemistry - Massachusetts Institute of Technology
- PhD 1992 Chemistry - University of California-Berkeley
- 718-432:Pharmaceutical Biochemistry
- 718-531:Medicinal Chemistry I
- 718-770:CNS Drug Design Action & Application I
- 718-771:CNS Drug Design Action & Application II
- 726-800:Responsible Conduct in Research
- Kopina, B., Missoury, S., Collinet, B., Fulton, M. G., Cirio, C., van Tilbeurgh, H., Lauhon, C. T. "Structure of a Reaction Intermediate Mimic in t6A Biosynthesis Bound in the Active Site of the TsaBD Heterodimer from Escherichia coli" (2021) Nucleic Acids Res., online ahead of print. PMID: 33524148
- Lauhon, C. T. "Identification and Characterization of Genes Required for the Biosynthesis of 5-Hydroxyuridine in Escherichia coli and Bacillus subtilis tRNA" (2019) J. Bacteriol. 201, 201(20):e00433-19.
- Neumann, P.; Lakomek, K.; Naumann P. T.; Erwin, W. M.; Lauhon, C. T.; Ficner, R. "Crystal Strucuture of a 4-Thiouridine Synthetase-RNA Complex Reveals Specificity of tRNA U8 Modification" (2014) Nuc. Acids Res. 42, 6673-6685.
- Naumann, P. T.; Lauhon, C. T.; Ficner, R. "Purification, Crystallization and Preliminary Crystallographic Analysis of a 4-Thiouridine Synthetase-RNA Complex" (2013) Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 69, 421-424.
- Shippy, D. C;. Eakley, N. M.; Lauhon, C. T.; Bochsler, P. N.; Fadl, A. A. "Virulence characteristics of Salmonella Following Deletion of Genes Encdoing the tRNA Modification Enzymes GidA and MnmE" (2013) Microb. Pathog. 57, 1-9.
- Lauhon, C. T. "Mechanism of N6-Threonylcarbamoyladenosine (t6A) Biosynthesis: Isolation and Characterization of the Intermediate Threonylcarbamoyl-AMP" (2012) Biochemistry 51, 8950-8963.
- Kopina, B. J.; Lauhon, C. T. "Efficient Preparation of 2,4-Diaminopyrimidine Nucleosides: Total Synthesis of Lysidine and Agmatidine" (2012) Org. Lett. 14, 4118-4121.
- Lauhon, C. T. "Orchestrating Sulfur Incorporation into RNA" (2006) Nat. Chem. Biol. 2, 182-183.
- Skovran, E.; Lauhon, C. T.; Downs, D. M. "Lack of YggX Results in Chronic Oxidative Stress and Uncovers Subtle Defects in Fe-S Cluster Metabolism in Salmonella enterica" (2004) J. Bacteriol. 186, 7626-7234.
- Lauhon, C. T., Erwin, W. M., Ton, G. N., "Substrate Specificity of 4-Thiouridine Biosynthesis in Escherichia coli," (2004) J. Biol. Chem., 279, 23022-23029.
- Lauhon, C. T.; Skovran, E.; Urbina, H.; Downs, D. M.; Vickery, L. E. "Substitutions in an Active Site Loop of Escherichia coli IscS Result in Specific Defects in Fe-S Cluster and Thionucleoside Biosynthesis in Vivo" (2004) J. Biol. Chem., 279, 19551-19558.
- Kambampati, R.; Lauhon, C. T. "MnmA and IscS are Required for In Vitro Biosynthesis of 2-Thiouridine in Escherichia coli" (2003) Biochemistry 42, 1109-1117.
- Wolfe, M. D., Ahmed, F., Lacourciere, G. M., Lauhon, C. T., Stadtman, T. C., Larson, T. J. "Functional diversity of the Rhodanese homology domain: The Escherichia coli ybbB gene encodes a selenophosphate-dependent tRNA 2-selenouridine synthase." (2004) J Biol Chem., 279, 1801-1809.
- C. T. Lauhon "Requirement for IscS in the Biosynthesis of All Thionucleosides in Escherichia coli" (2002) J. Bacteriol. 284, 6820-6829.
- R. Kambampati and C. T. Lauhon, "The NifS-Like Protein of Escherichia coli is Involved in the Biosynthesis of 4-Thiouridine in tRNA" (1999) Biochemistry 38, 16561-16568.
- C. T. Lauhon and R. Kambampati "The iscS Gene in Escherichia coli is Required for the Biosynthesis of 4-Thiouridine, Thiamin and NAD" (2000) J. Biol. Chem. 275, 20096-20113.
- R. Kambampati and C. T. Lauhon "Evidence for the Transfer of Sulfane Sulfur from IscS to ThiI during the in Vitro Biosynthesis of 4-Thiouridine in Escherichia coli tRNA" (2000) J. Biol. Chem. 275, 10727-10730.