| First Author | Meharena HS | Year | 2016 |
| Journal | PLoS Biol | Volume | 14 |
| Issue | 11 | Pages | e2000127 |
| PubMed ID | 27902690 | Mgi Jnum | J:239850 |
| Mgi Id | MGI:5881869 | Doi | 10.1371/journal.pbio.2000127 |
| Citation | Meharena HS, et al. (2016) Decoding the Interactions Regulating the Active State Mechanics of Eukaryotic Protein Kinases. PLoS Biol 14(11):e2000127 |
| abstractText | Eukaryotic protein kinases regulate most cellular functions by phosphorylating targeted protein substrates through a highly conserved catalytic core. In the active state, the catalytic core oscillates between open, intermediate, and closed conformations. Currently, the intramolecular interactions that regulate the active state mechanics are not well understood. Here, using cAMP-dependent protein kinase as a representative model coupled with biochemical, biophysical, and computational techniques, we define a set of highly conserved electrostatic and hydrophobic interactions working harmoniously to regulate these mechanics. These include the previously identified salt bridge between a lysine from the beta3-strand and a glutamate from the alphaC-helix as well as an electrostatic interaction between the phosphorylated activation loop and alphaC-helix and an ensemble of hydrophobic residues of the Regulatory spine and Shell. Moreover, for over three decades it was thought that the highly conserved beta3-lysine was essential for phosphoryl transfer, but our findings show that the beta3-lysine is not required for phosphoryl transfer but is essential for the active state mechanics. |
