Format

Send to

Choose Destination
Bioinformation. 2019 Oct 13;15(9):666-677. doi: 10.6026/97320630015666. eCollection 2019.

Insights into evolutionary interaction patterns of the 'Phosphorylation Activation Segment' in kinase.

Author information

1
Modeling and Molecular Spectroscopy Team, Faculty of Sciences, University Chouaib Doukkali, El-Jadida, Morroco.
2
Analytical Chemistry and Environmental Sciences Team, Department of chemistry, Faculty of Science, University Chouaib Doukkali, El Jadida, Morroco.
3
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia.
4
Extraction, Spectroscopy and Valorization Team, Organic synthesis, Extraction and Valorization Laboratory, Faculty of Sciences of Ain Chock, Hassan II University, Casablanca, Morocco.

Abstract

We are interested in studying the phosphorylation of the kinase activation loop, distinguishing the passage from the unphosphorylated to the phosphorylated form without allostery. We performed an interaction study to trace the change of interactions between the activation segment and the kinase catalytic core, before and after phosphorylation. Results show that the structural changes are mainly due to the attraction between the phosphate group and guanidine groups of the arginine side chains of RD-pocket, which are constituted mainly of guanidine groups of the catalytic loop, the β9, and the αC helix. This attraction causes propagation of structural variation of the activation segment, principally towards the N-terminal. The structural variations are not made on all the amino acids of the activation segment; they are conditioned by the existence of two beta sheets stabilizing the loop during phosphorylation. The first,β6-β9 sheet is usually present in most of the kinases; the second, β10-β11 is formed due to the interaction between the main chain amino acids of the activation loop and the αEF/αF loop.

KEYWORDS:

Kinase; activation segment; interaction variation; phosphorylation; structural variation

Conflict of interest statement

The authors declare that they have no conflict of interest.

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center