title: Theoretical Investigation of the Mechanisms of ERK2 Enzymatic Catalysis.
abstract: ERK2 are protein kinases that during the enzymatic catalysis, in contrast to traditional enzymes, utilize additional interactions with substrates outside of the active sites. It is widely believed that these docking interactions outside of the enzymatic pockets enhance the specificity of these proteins. However, the molecular mechanisms of how the docking interactions affect the catalysis remain not well understood. Here, we develop a simple theoretical approach to analyze the enzymatic catalysis in ERK2 proteins. Our method is based on first-passage process analysis, and it provides explicit expressions for all dynamic properties of the system. It is found that there are specific binding energies for substrates in docking and catalytic domains that lead to maximal enzymatic reaction rates. Thus, we propose that the role of the docking interactions is not only to increase the enzymatic specificity but also to optimize the dynamics of the catalytic process. Our theoretical results are utilized to describe experimental observations on ERK2 enzymatic activities.
authors.affiliation: Department of Chemistry and Center for Theoretical Biological Physics, Rice University , Houston, Texas 77005, United States.
authors.forename: Mikita M
authors.initials: MM
authors.lastname: Misiura
authors.affiliation: Department of Chemistry and Center for Theoretical Biological Physics, Rice University , Houston, Texas 77005, United States.
authors.forename: Anatoly B
authors.initials: AB
authors.lastname: Kolomeisky
mesh_terms: D001665:Binding Sites; D055162:Biocatalysis; D020134:Catalytic Domain; D007700:Kinetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry / Q000378:metabolism*; D062105:Molecular Docking Simulation; D010766:Phosphorylation; D013379:Substrate Specificity
chemical_list: D019950:Mitogen-Activated Protein Kinase 1