The goal of our research is to understand how nucleic acids and their constituents interact with one another, with proteins and with drugs. Specifically, we continue to examine the role of sequence, chemical modifications and environment on the structures and on their interactions. The principal method of analysis is x-ray crystallographic studies of the structures of selected oligonucleotides and complexes of oligonucleotides with drugs. The oligonucleotides chosen contain biologically relevant sequences, mutagenic and carcinogenic lesions, and features that allow for the formation of hairpins and cruciforms. We will complete the analysis of a complex between the chemotherapeutic drug, Actinomycin D and a small fragment of DNA to which it is known to bind. We will also continue pilot studies on the nucleotide binding enzyme, AMP nucleosidase with the goal of producing crystals suitable for a full x-ray crystallographic analysis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM021589-19
Application #
3270590
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1989-12-01
Project End
1994-11-30
Budget Start
1992-12-01
Budget End
1993-11-30
Support Year
19
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Rutgers University
Department
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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