The solution structure of Abl SH3, and its relationship to SH2 in the SH(32) construct.

摘要: Abstract Background: The Src homology domains, SH3 and SH2, of Abl protein tyrosine kinase regulate enzymatic activity in vivo. suppresses activity, whereas SH2 is required for the transforming activated form Abl. We expect that solution structures SH3, SH(32) (a dual domain comprising subdomains) will contribute to a structural basis understanding mechanism ‘regulatory apparatus'. Results present structure free characterization regulatory apparatus, domain. was determined using multidimensional double resonance NMR spectroscopy. It consists two antiparallel β sheets packed orthogonally, an arrangement first shown spectrin SH3. Compared with crystal complexed natural ligand, there no significant difference overall folding pattern. characterized by spectroscopy 1 H 15 N assignment SH2. On high degree similarity chemical shifts hydrogen/deuterium exchange pattern individual domains compared those domain, model apparatus suggested. This good agreement ligand-binding characteristics SH(32). binding constants isolated when ligands, measured intrinsic fluorescence quenching, do not differ significantly from these within Conclusion SH(32), provide information about topology modular domains. monomer, connected flexible linker. Sites ligand subdomains are independent.