7uis

Cocrystal structure of human CaMKII-alpha (CAMK2A)kinase domain and GluN2B(S1303D)Cocrystal structure of human CaMKII-alpha (CAMK2A)kinase domain and GluN2B(S1303D)

Structural highlights 7uis is a 2 chain structure. This structure supersedes the now removed PDB entry 7kl4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 6xoe Activity: Calcium/calmodulin-dependent protein kinase, with EC number 2.7.11.17 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [NMDE2_HUMAN] Autosomal dominant non-syndromic intellectual disability;West syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberrations involving GRIN2B has been found in patients with mental retardation. Translocations t(9;12)(p23;p13.1) and t(10;12)(q21.1;p13.1) with a common breakpoint in 12p13.1. Function [KCC2A_HUMAN] CaM-kinase II (CAMK2) is a prominent kinase in the central nervous system that may function in long-term potentiation and neurotransmitter release. Member of the NMDAR signaling complex in excitatory synapses it may regulate NMDAR-dependent potentiation of the AMPAR and synaptic plasticity (By similarity). [NMDE2_HUMAN] NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death (By similarity). Publication Abstract from PubMed Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a signaling protein required for long-term memory. When activated by Ca(2+)/CaM, it sustains activity even after the Ca(2+) dissipates. In addition to the well-known autophosphorylation-mediated mechanism, interaction with specific binding partners also persistently activates CaMKII. A long-standing model invokes two distinct S and T sites. If an interactor binds at the T-site, then it will preclude autoinhibition and allow substrates to be phosphorylated at the S site. Here, we specifically test this model with X-ray crystallography, molecular dynamics simulations, and biochemistry. Our data are inconsistent with this model. Co-crystal structures of four different activators or substrates show that they all bind to a single continuous site across the kinase domain. We propose a mechanistic model where persistent CaMKII activity is facilitated by high-affinity binding partners that kinetically compete with autoinhibition by the regulatory segment to allow substrate phosphorylation. CaMKII binds both substrates and activators at the active site.,Ozden C, Sloutsky R, Mitsugi T, Santos N, Agnello E, Gaubitz C, Foster J, Lapinskas E, Esposito EA, Saneyoshi T, Kelch BA, Garman SC, Hayashi Y, Stratton MM Cell Rep. 2022 Jul 12;40(2):111064. doi: 10.1016/j.celrep.2022.111064. PMID:35830796 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Calcium/calmodulin dependent protein kinase 3D structures Glutamate receptor 3D structures

spinqualitylabelsall models 7uis, resolution 2.58Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image