The goals of this research are to determine the principles that underlie the interactions of key biological molecules. We will use the methods of x-ray crystallography to determine the three dimensional structures of selected molecules. In order to understand how nucleic acids interact with one another, with water, with drugs and with proteins we will determine the crystal structures of selected defined sequence oligonucleotides including ones that contain mutagenic and carcinogenic modifications. We will also determine the crystal structures of complexes between wildtype and mutant Catabolite Activating Protein (CAP) and selected variants of the consensus DNA sequence. The results of these will be analyzed to understand the biochemical and thermodynamic data that have been collected for this system. Collagen is an important structural protein whose principal structural element is the triple helix. Triple helices are also found in certain parts of globular proteins. We plan to determine the structures of a series of model collagen peptides with the goal of understanding how collagen assembles and interacts with other molecules in its environment.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM021589-21
Application #
2173757
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1989-12-01
Project End
1998-11-30
Budget Start
1994-12-01
Budget End
1995-11-30
Support Year
21
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Rutgers University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
038633251
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901
Rao, Ramya R; Lawson, Catherine L (2014) Structure of catabolite activator protein with cobalt(II) and sulfate. Acta Crystallogr F Struct Biol Commun 70:560-3
Carey, Jannette; Benoff, Brian; Harish, Balasubramanian et al. (2012) Environment-dependent long-range structural distortion in a temperature-sensitive point mutant. Protein Sci 21:63-74
Lara-Gonzalez, Samuel; Birktoft, Jens J; Lawson, Catherine L (2010) Structure of the Escherichia coli RNA polymerase alpha subunit C-terminal domain. Acta Crystallogr D Biol Crystallogr 66:806-12
Hudson, Brian P; Quispe, Joel; Lara-Gonzalez, Samuel et al. (2009) Three-dimensional EM structure of an intact activator-dependent transcription initiation complex. Proc Natl Acad Sci U S A 106:19830-5
Locasale, Jason W; Napoli, Andrew A; Chen, Shengfeng et al. (2009) Signatures of protein-DNA recognition in free DNA binding sites. J Mol Biol 386:1054-65
Bella, Jordi; Liu, Jingsong; Kramer, Rachel et al. (2006) Conformational effects of Gly-X-Gly interruptions in the collagen triple helix. J Mol Biol 362:298-311
Napoli, Andrew A; Lawson, Catherine L; Ebright, Richard H et al. (2006) Indirect readout of DNA sequence at the primary-kink site in the CAP-DNA complex: recognition of pyrimidine-purine and purine-purine steps. J Mol Biol 357:173-83
Tuske, Steven; Sarafianos, Stefan G; Wang, Xinyue et al. (2005) Inhibition of bacterial RNA polymerase by streptolydigin: stabilization of a straight-bridge-helix active-center conformation. Cell 122:541-52
Berman, Helen M; Ten Eyck, Lynn F; Goodsell, David S et al. (2005) The cAMP binding domain: an ancient signaling module. Proc Natl Acad Sci U S A 102:45-50
Lawson, Catherine L; Swigon, David; Murakami, Katsuhiko S et al. (2004) Catabolite activator protein: DNA binding and transcription activation. Curr Opin Struct Biol 14:10-20

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