Abstract

The long term goals of this research are to understand the structural basis of the large non-receptor protein tyrosine kinase from the Abelson gene, Ab1. We wish to understand the nature of its interactions with extra-Ab1 ligands, and the possible intra-Ab1 interactions among the several protein domains. Concentrating on possible structural correlates of the transforming potential of Ab1, a protooncogene product, the structure and dynamics, studied by high resolution NMR, of ligated domains of the SH2 and SH3 of Ab1, and a combined construct,SH(3/2) will be determined. Ab1 itself may use other SH2 and SH3 containing proteins to modify its activities in signal transducing particles, in its possibly multiple roles. Based on the identification of sites for other SH3's to bind to Ab1, peptide ligands have been made imitating these segments and the structure and dynamics of these segments bound to non-Ab1 SH3's will be determined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM047021-04A1
Application #
2184501
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
1992-02-01
Project End
1999-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
4
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
Rockefeller University
Department
Chemistry
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Liu, Dongsheng; Yuan, Ya; Xu, Rong et al. (2017) Domain interactions of C-terminal Src Kinase determined through NMR spectroscopy with segmental isotope labeling. Protein Cell 8:67-71
Ferrage, Fabien; Dutta, Kaushik; Cowburn, David (2015) Identification of Hydrophobic Interfaces in Protein-Ligand Complexes by Selective Saturation Transfer NMR Spectroscopy. Molecules 20:21992-9
Bhattacharya, Shibani; Ju, Jeong Ho; Orlova, Natalia et al. (2013) Ligand-induced dynamic changes in extended PDZ domains from NHERF1. J Mol Biol 425:2509-28
Xu, Rong; Liu, Dongsheng; Cowburn, David (2012) Abl kinase constructs expressed in bacteria: facilitation of structural and functional studies including segmental labeling by expressed protein ligation. Mol Biosyst 8:1878-85
Kalinina, Juliya; Dutta, Kaushik; Ilghari, Dariush et al. (2012) The alternatively spliced acid box region plays a key role in FGF receptor autoinhibition. Structure 20:77-88
Piserchio, Andrea; Cowburn, David; Ghose, Ranajeet (2012) Expression and purification of Src-family kinases for solution NMR studies. Methods Mol Biol 831:111-31
Bhattacharya, Shibani; Zhang, Hongtao; Cowburn, David et al. (2012) Novel structures of self-associating stapled peptides. Biopolymers 97:253-64
Zhang, Hongtao; Curreli, Francesca; Zhang, Xihui et al. (2011) Antiviral activity of ?-helical stapled peptides designed from the HIV-1 capsid dimerization domain. Retrovirology 8:28
Ferrage, Fabien; Reichel, Amy; Battacharya, Shibani et al. (2010) On the measurement of ¹?N-{¹H} nuclear Overhauser effects. 2. Effects of the saturation scheme and water signal suppression. J Magn Reson 207:294-303
Tait, Shirley; Dutta, Kaushik; Cowburn, David et al. (2010) Local control of a disorder-order transition in 4E-BP1 underpins regulation of translation via eIF4E. Proc Natl Acad Sci U S A 107:17627-32

Showing the most recent 10 out of 58 publications