This entry includes the alpha-protein kinase 1, a serine/threonine-protein kinase that has no homology to conventional protein kinases and phosphorylate amino acids located within α-helices []. The N-terminal region had several conserved secondary α-helix structures with amphipathic properties []. The structure contains 18 helices (α1 to α18), forming seven antiparallel pairs. The one-by-one-packed seven helix pairs form a right-hand solenoid, similar to the tetratricopeptide repeat (TPR) domain structure [].This kinase detects bacterial pathogen-associated molecular pattern metabolites (PAMPs) and initiates an innate immune response, a critical step for pathogen elimination and engagement of adaptive immunity. Specifically recognises and binds ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria. ADP-Heptose binds to a narrow pocket of the concave side of the alpha-protein kinase 1 N-terminal which stimulates its kinase activity to phosphorylate and activate TIFA, triggering proinflammatory NF-kappa-B signalling [, ]. In addition, alpha-protein kinase 1 may play a role in regulating intracellular trafficking processes through the phosphorylation of myosin MYO1A []. It has been shown that this kinase is also involved in monosodium urate monohydrate (MSU)-induced inflammation and gout by phosphorylation of myosin motor protein which enable the vesicle transport of of certain cytokines (like TNF-alpha) to the plasma membrane [].
