Structural modeling of the catalytic subunit-regulatory subunit dimeric complex of the camp-dependent protein kinase.
- Chang-Shung
- Stephen C.
- Donal A.
- Jill
The cAMP-dependent protein kinase (PKA) is a multifunctional kinase that serves as a prototype for understanding second messenger signaling and protein phosphorylation. In the absence of a cAMP signal, PKA exists as a dimer of dimers, consisting of two regulatory (R) and two catalystic (C) subunits. Based on experimentally derived data (i.e., crystal structures of the R and C subunits, mutagenesis data identifying points of subunit-subunit contacts), the neutron scattering derived model for the heterodimer (Zhao et al., 1998) and using a set of computational approaches (homology modeling, Monte Carlo simulation), they have developed a high-resolution model of the RII{alpha}-C{alpha} dimer. The nature of the subunit-subunit interface was studied. The model reveals an averaged size dimer interface (2100 Angstrom{sup 2}) that is distant from the pseudo-substrate binding site on the C subunit. The additional contacts made by the pseudosubstrate increases the stability of the dimeric complex. Based on a set of R-C dimer structures derived using a simulated annealing approach, specific interactions (hydrogen bonds) between the two subunits and were identified.
- Research Organization:
- Los Alamos National Laboratory
- Sponsoring Organization:
- DOE
- OSTI ID:
- 975141
- Report Number(s):
- LA-UR-01-0963; LA-UR-01-963
- Country of Publication:
- United States
- Language:
- English
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