Abstract

The lactose operon has served as the paradigm to study gene regulation. To understand more completely how the operon is regulated we have undertaken the crystallographic structure determination of (1) the lac repressor, (2) the repressor bound to inducer and (3) the repressor in a ternary complex with synthetic operator fragments of DNA plus an anti-inducer. The three dimensional structure of this protein and the complexes will allow us to address such questions as: (1) How does the repressor recognize specific sites on the DNA? (2) How do the inducers and anti-inducers affect the conformation of the repressor? (3) What role does structure play in the allosteric mechanism and how is it used to regulate gene expression? In addition, the three dimensional structure of the lac repressor will provide a framework for correlating and interpreting an extensive body of genetic and chemical data.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM044617-03
Application #
3303818
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1990-07-01
Project End
1993-07-31
Budget Start
1992-07-01
Budget End
1993-07-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

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) 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; 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; 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

Showing the most recent 10 out of 11 publications