EXCEED THE SPACE PROVIDED. The long-range goal of our research is to understand the structural basis of gene regulation and how repressors, activators, and anti-terminators regulate transcription. Over the years we have focused on the two paradigms, the lactose operon of E-coli and the 'genetic switch' of bacteriophage lambda. This grant originally funded the three-dimensional structure determination of the intact lac repressor, the lac repressor bound to the gratuitous inducer 1-isopropyl-_-D-thiogalactoside (IPTG) and the lac repressor complexed with a 21 base-pair symmetric operator DNA. These three structures have provided a detailed structural model for repressor in the induced and the repressed states, and a framework for understanding a wealth of biochemical and genetic information (Lewis et al., 1996). Building upon these results, we designed new experiments and solved structures to probe more deeply the function of this protein. In this last granting period, we also resumed earlier studies of the repressor from phage lambda (Bell et al., 2000) and provided structural insight as to the molecular basis of this genetic switch. In this funding period, we plan to continue our studies on proteins that regulate transcription.The long-range goal of our research is to understand the structural basis of gene regulation and how repressors, activators, and anti-terminators regulate transcription. PERFORMANCE SITE ========================================Section End===========================================
| Daber, Robert; Sochor, Matthew A; Lewis, Mitchell (2011) Thermodynamic analysis of mutant lac repressors. J Mol Biol 409:76-87 |
| Lewis, Mitchell (2011) A tale of two repressors. J Mol Biol 409:14-27 |
| Milk, Leslie; Daber, Robert; Lewis, Mitchell (2010) Functional rules for lac repressor-operator associations and implications for protein-DNA interactions. Protein Sci 19:1162-72 |
| Daber, Robert; Lewis, Mitchell (2009) A novel molecular switch. J Mol Biol 391:661-70 |
| Hochschild, Ann; Lewis, Mitchell (2009) The bacteriophage lambda CI protein finds an asymmetric solution. Curr Opin Struct Biol 19:79-86 |
| Daber, Robert; Lewis, Mitchell (2009) Towards evolving a better repressor. Protein Eng Des Sel 22:673-83 |
| Daber, Robert; Sharp, Kim; Lewis, Mitchell (2009) One is not enough. J Mol Biol 392:1133-44 |
| Daber, Robert; Stayrook, Steven; Rosenberg, Allison et al. (2007) Structural analysis of lac repressor bound to allosteric effectors. J Mol Biol 370:609-19 |
| Lewis, M; Chang, G; Horton, N C et al. (1996) Crystal structure of the lactose operon repressor and its complexes with DNA and inducer. Science 271:1247-54 |
| Hoog, S S; Pawlowski, J E; Alzari, P M et al. (1994) Three-dimensional structure of rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase: a member of the aldo-keto reductase superfamily. Proc Natl Acad Sci U S A 91:2517-21 |
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