CAMK1G: Human Ca2+/calmodulin-dependent protein kinase I-gamma
PDB Code: 2JAM
The Ser/Thr kinases Ca2+/calmodulin-dependent protein kinase I (CaMKI) constitutes a family of closely related isoforms (alpha, beta and gamma). CaMK isoforms play a critical role in establishing distinct types of memory in mammals. The activation of CAMK1G requires binding of Ca 2+/ CaM and phosphorylation by other kinases, presumably by a CaMKK.
CAMK1G expression is first detectable at embryonic day 11 (E11) and it is predominantly expressed in neurons but not glia. Within the CNS, highest expression is found in the forebrain neocortex (cerebral cortex, occipital pole, frontal lobe, and temporal lobe), the striatum (putamen and caudate nucleus), and the limbic system (amygdale and hippocampus). CAMK1G expression is altered in response to brain-derived neurotrophic factor (BDNF).
Here we present the structure of CaMK1G in complex with the ATP competitive inhibitor 5-[(Z)- (5-Chloro -2-oxo-1,2- dihydro- 3H-indol- 3-ylidene) methyl]-N- [2-(diethylamino) ethyl]-2,4- dimethyl-1H- pyrrole-3- carboxamide. This inhibitor has been initially described as a tyrosine kinase receptor and angiogenic inhibitor that exhibits selectivity for PDGFRb (IC50= 3 nM), VEGFR2 (IC50= 27 nM), FGFR1 (IC50= 170 nM), and Kit family members (IC50~ 10-500 nM) over EGFR (IC50>20 µM). This inhibitor has been reported to display anti-proliferative and pro-apoptotic properties in tumor cells.

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