Bioinformatic analyses of P. falciparum eIF2α kinases. A: Phylogenetic tree showing clustering of PfeIF2α kinases with human eIF2α kinases. Sequences: PfeIK1: PF14_0114; PfeIK2: PFA0380w; PfPK4: PFF1370; PKR: GI:4506103; HRI: GI:6580979; PERK: GI:18203329; GCN2: GI:65287717; MEK1: GI:400274; IRAK1: GI:68800243; Aurora: GI:37926805; CDK2: GI:1942427; PfCK1: PF11_0377; PfNEK2: Pfe1290w; PfPK5: MAL13P1.279; PfPKA: PFI1685w; PFTKL3: PF13_0258; Pfb0815w: PfCDPK1; hCAMK1: GI:4502553; hPRKACA: GI:46909584; hCSNK1d: GI:20544145; hNEK7: GI:19424132; hSRC: GI:4885609. B. Alignment of the catalytic domains of PfeIK1, PbeIK1 and human GCN2. Identical residues in all three kinases are in black boxes, residues that are identical in two sequences of the three sequences, or that are similar are boxed in grey. The number of residues comprising the inserts between domains IV and V are marked between //-//. Asterisks (*) mark residues conserved among kinases in general, while open arrowheads (∨) indicate residues specifically conserved among eIF2α kinases. The downwards arrow marks the threonine residues that are targets for autophosphorylation in GCN2. PlasmoDB accession numbers: PfeIK1: PF14_0423, PbeIK1: PB000582.03.0 GenBank accession number: HsGCN2: GI:65287717. C: Schematic of the domain structures of PfeIK1, PbeIK1 and GCN2. Kinase domains (KD) are in grey, hatched regions represent the inserts (I) within the kinase domains and regions with no identified function are white. Additional characterized domains of GCN2 are as follows: red; N-terminal GCN1 binding domain (GB), green; pseudo-kinase domain (ΨKD), blue; histidyl-tRNA synthetase (HisRS), yellow; ribosome binding and dimerisation domain (RB/DD).