title: Interaction of peptide substrate outside the active site influences catalysis by CaMKII.
abstract: The interaction of calcium/calmodulin-dependent protein kinase II (CaMKII) with the NR2B subunit of N-methyl-D-aspartate-type glutamate receptor is thought to be one of the important events leading to synaptic plasticity. CaMKII binds NR2B by its catalytic site and by the autophosphorylation site binding pocket (APBP), a non-catalytic site. Mutagenesis of Glu-236, a residue in the APBP of CaMKII that is likely to be interacting with NR2B, influences phosphorylation of NR2B. The phosphorylation of syntide-2, a classical catalytic site substrate of CaMKII, is influenced to a much lesser extent by this mutation. Taken together these results indicate that interaction of NR2B at the non-catalytic site of CaMKII influences catalysis. Our data suggest that kinetic models of peptide substrate phosphorylation by CaMKII should incorporate the non-catalytic mode of binding of peptides that is dependent on the sequence of the peptide.
authors.affiliation: Rajiv Gandhi Centre for Biotechnology, Thycaud P.O., Thiruvananthapuram, Kerala-695014, India.
authors.forename: M
authors.initials: M
authors.lastname: Praseeda
authors.forename: M
authors.initials: M
authors.lastname: Mayadevi
authors.forename: R V
authors.initials: RV
authors.lastname: Omkumar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002384:Catalysis; D020134:Catalytic Domain; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C121001:NR2B NMDA receptor; D010455:Peptides; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; C063391:syntide-2; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases