CLK coordination of substrate-binding and catalytic regions. Interactions between key residues in the substrate-binding region and the catalytic HTD motif are mediated by conserved residues in the activation loop. (A) Structural context of features in PfLAMMER [PDB:3LLT], showing the activation loop in green and the catalytic loop in magenta. Conserved residues are displayed in "sticks" representation. A contrastingly conserved asparagine, distinctive of chromalveolate CLKs, is indicated in cyan, and three other residues conserved throughout the CLK family are shown in yellow. (B) In PfLAMMER, the distinctive asparagine (N736) forms hydrogen bonds with the CMGC-conserved arginine (R741), the backbone of the alanine in the APE motif, the backbone of the threonine in the catalytic HTD motif, and, mediated by a water molecule, a subfamily-conserved serine in the αF helix. (C) In human SRPK1, several of the hydrogen bonds formed by the glutamine Q513 are analogous to those formed by the N736 in apicomplexans. (D) and (E) Two structures of human Clk1. In the unphosphorylated structure [PDB:1Z57], left, the serine corresponding to PfLAMMER N736 (S341) and the adjacent CLK-conserved threonine (T342) are oriented in an "in" conformation, interacting with the catalytic motif (HTD) but not with the conserved arginines (R343, R346). In the phosphorylated structure [PDB:2VAG], right, the serine (pS341) and threonine (pT342) are flipped to an "out" conformation, breaking the interaction with the catalytic motif. One arginine (R343) moves to occupy the area vacated by the phosphorylated serine S341, while the other (R346) now interacts with the backbone of the phosphorylated serine. Phosphates are shown in orange. Images of PDB structures were rendered using PyMOL .
Talevich et al. BMC Evolutionary Biology 2011 11:321 doi:10.1186/1471-2148-11-321