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Research Focus

Our goal is to develop a high-throughput and cost-effective structure pipeline and to utilize it to determine novel protein folds and to explore protein structure/function relationships. We have applied this approach to the extensive study of the thermophilic bacterium Thermotoga maritima, as well as, targets from mouse and over 100 bacterial genomes. Our technologies have allowed us to perform comprehensive structural studies of these proteomes. To date, these efforts have resulted in over 500 novel protein structures at a current rate of ~175 structures per year. Furthermore, we have used structural data and performed biochemical assays to validate predicted activities and determine function for numerous targets for which no function could be predicted.

Selected References

Eshaghi S, Niegowski D, Kohl A, Martinez Molina D, Lesley SA, Nordlund P. Crystal structure of a divalent metal ion transporter CorA at 2.9 angstrom resolution. Science. 2006 Jul 21;313(5785):354-7.

Columbus L, Lipfert J, Klock H, Millett I, Doniach S, Lesley SA. Expression, purification, and characterization of Thermotoga maritima membrane proteins for structure determination. Protein Sci. 2006 May;15(5):961-75.

McMullan D, Canaves JM, Quijano K, Abdubek P, Nigoghossian E, Haugen J, Klock HE, Vincent J, Hale J, Paulsen J, Lesley SA. High-throughput protein production for X-ray crystallography and use of size exclusion chromatography to validate or refute computational biological unit predictions. J. Struct. Funct. Genomics. 2005;6(2-3):135-41.

Spraggon G, Pantazatos D, Klock HE, Wilson IA, Woods VL, Lesley SA. On the use of DXMS to produce more crystallizable proteins: structures of the T. maritima proteins TM0160 and TM1171. Protein Sci. 2004 Dec;13(12):3187-99.