(656.6) Effects of Phosphorylation of ERK2 Kinase on the Properties of Active Site Amino Acids

Poster Board Number: A188

Joie Sun (Northeastern University), J. Max Trumble (Northeastern University), Kelly Barnsley (Northeastern University), Mary Jo Ondrechen (Northeastern University)

ERK2 is a mitogen-activated protein kinase and is also called MAPK1. ERK2 is activated by phosphorylation at the side chains of two amino acids, Threonine 183 (T183) and Tyrosine 185 (Y185). Activation is accompanied by a conformational change. Upon activation, ERK2 enters the cell nucleus, where it carries signals involved in the regulation of cell proliferation, differentiation, and apoptosis. X-ray crystal structures are available for both the phosphorylated (active) and unphosphorylated (inactive) conformations. Using computed electrical potential functions from numerical solutions to the Poisson-Boltzmann equations and analysis with Partial Optimum Order Likelihood (POOL), electrostatic properties of the active site amino acids are calculated for both conformations. Changes in the proton transfer properties of active site amino acids D147, K149, and D165 are predicted. While structural and dynamic changes are known to be part of the activation of ERK2, the present results suggest that interactions with the phosphorylated amino acids also facilitate enzymatic activity. These electrostatic properties give insight into how phosphorylation controls the catalytic properties of ERK2.

Support or Funding Information

Supported by NSF CHE-1905214 and a Fulbright Faculty Research Award (MJO).

lt;pgt;Supported by NSF CHE-1905214 and a Fulbright Faculty Research Award (MJO). amp;nbsp;lt;/pgt;



Aligned structures of doubly-phosphorylated ERK2 (PDB ID 6OPG) in magenta and unphosphorylated ERK2 (PDB ID 4GT3) in cyan; the bound ATP molecules are rendered as balls.