FIG 5.

Alignments of ER-resident eIF2α kinase domains. The sequences of the kinase domains of Toxoplasma gondii TgIF2K-A, Plasmodium falciparum PfPK4, mouse PERK, and human PERK were aligned using the ClustalW program. Residues highlighted in black are identical or similar among all four species, and those displaying sequence divergence among individuals of a single species are highlighted in gray. Motifs comprising the kinase domain are designated I to XI. The catalytic lysine (K) in subdomain II and the DFG motif in subdomain VII, which plays an important role in the regulation of kinase activity, are enclosed in black boxes. The methionine (M) gatekeeper residue inside subdomain V is indicated with a black arrow. Amino acid residues in the hinge are indicated with asterisks, and back-pocket regions of the active site critical for binding of PERKi are boxed in gray. The sequences of TgIF2K-A (ToxoDB accession number TGGT1_229630), PfPK4 (PlasmoDB accession number PF3D7_0628200), mouse PERK (E2AK3_MOUSE-Mus musculus, gene ID 13666), and human PERK (E2AK3_HUMAN-Homo sapiens, gene ID 9451) were obtained from the indicated databases.