The general goal of this project is to investigate the energetic basis of all levels of protein structure including specific protein complexes, and determine experimentally the factors responsible for their formation. This requires: (a) estimation of the overall energetic balance of formation of macromolecular structures in aqueous solution by microcalorimetric techniques, and (b) estimation of the hydration component of these energetics by studying the transfer of various compounds modeling protein groups into water. Previously, Dr. Privalov concentrated on studies of the energetics of formation of tertiary structure of globular proteins. He now proposes to extend this approach to the investigation of two other levels of protein structure: the lower level, secondary structure, which will be modeled by synthetic polypeptides, and the higher level, the quaternary structure and specific complexes of proteins with proteins and nucleic acids. Covering all levels of protein structure is required to refine the previously obtained parameters, to investigate the interaction between the various levels of structural organization, and to clarify the physical basis of molecular recognition in biology.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM048036-08
Application #
6018907
Study Section
Special Emphasis Panel (ZRG3-BBCA (01))
Project Start
1992-08-01
Project End
2000-07-31
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Privalov, Peter L; Dragan, Anatoly I; Crane-Robinson, Colyn (2009) The cost of DNA bending. Trends Biochem Sci 34:464-70
Crane-Robinson, Colyn; Dragan, Anatoly I; Read, Christopher M (2009) Defining the thermodynamics of protein/DNA complexes and their components using micro-calorimetry. Methods Mol Biol 543:625-51
Dragan, Anatoly I; Privalov, Peter L (2008) Use of fluorescence resonance energy transfer (FRET) in studying protein-induced DNA bending. Methods Enzymol 450:185-99
Privalov, Peter L; Dragan, Anatoly I (2007) Microcalorimetry of biological macromolecules. Biophys Chem 126:16-24
Privalov, Peter L; Dragan, Anatoly I; Crane-Robinson, Colyn et al. (2007) What drives proteins into the major or minor grooves of DNA? J Mol Biol 365:1-9
Crane-Robinson, Colyn; Dragan, Anatoly I; Privalov, Peter L (2006) The extended arms of DNA-binding domains: a tale of tails. Trends Biochem Sci 31:547-52
Dragan, Anatoly I; Li, Zhenlan; Makeyeva, Elena N et al. (2006) Forces driving the binding of homeodomains to DNA. Biochemistry 45:141-51
Hargreaves, Victoria V; Makeyeva, Elena N; Dragan, Anatoly I et al. (2005) Stability and DNA binding ability of the DNA binding domains of interferon regulatory factors 1 and 3. Biochemistry 44:14202-9
Dragan, Anatoly I; Frank, Leslie; Liu, Yingyun et al. (2004) Thermodynamic signature of GCN4-bZIP binding to DNA indicates the role of water in discriminating between the AP-1 and ATF/CREB sites. J Mol Biol 343:865-78
Dragan, Anatoly I; Liu, Yingyun; Makeyeva, Elena N et al. (2004) DNA-binding domain of GCN4 induces bending of both the ATF/CREB and AP-1 binding sites of DNA. Nucleic Acids Res 32:5192-7

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