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. Author manuscript; available in PMC: 2010 Apr 9.
Published in final edited form as: Mol Cell. 2008 Mar 14;29(5):563–576. doi: 10.1016/j.molcel.2007.12.017

Figure 4. RS Domain and Phosphoserine Binding to Kinase.

Figure 4

(A) The RS peptide from ASF/SF2 binds to the SRPK1 docking groove in an extended conformation. (Left) The docking peptide extends from residue 201 to 210. Residues R204, R206, S207, and R210 of the substrate and Y181, N182, T546, D548, L550, E571, D564, W606, and K615 of the kinase are involved in the binding interaction. The side chain of R208 is disordered, and only the main chain and Cβ atom are modeled. (Right) A 9-mer peptide, derived from the phosphorylation site of the yeast SR-like protein Npl3p, is involved in similar interactions with the kinase-docking groove, as described previously (Ngo et al., 2005). Hydrogen bonds are depicted by dotted lines.

(B) Comparison of phosphor-interacting sites in SRPK1 and other kinases. (Top) The phosphoserine (P-Ser) docks to a basic (P+2) pocket of SRPK1. The location of the pocket in the context of the entire kinase is shown on the left. Three basic residues from two different secondary structural elements (P+1 loop and helix αG) converge, forming a positively charged pocket (right). (Middle) Phosphothreonine (T197) of PKA stabilizes a basic cluster formed by R165, K189, and H87 and is important to the activation of the kinase (Knighton et al., 1991). (Bottom) A phosphate ion binds to a basic pocket at the activation segment of GSK3β and mimics the phosphate group of a primed phosphoserine in the substrate that facilitates substrate binding and activation of the kinase (ter Haar et al., 2001).