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Review
. 2007 Nov;107(11):5065-81.
doi: 10.1021/cr068221w. Epub 2007 Oct 19.

Substrate and docking interactions in serine/threonine protein kinases

Elizabeth J Goldsmith  1 , Radha Akella, Xiaoshan Min, Tianjun Zhou, John M Humphreys
Affiliations
Review

Substrate and docking interactions in serine/threonine protein kinases

Elizabeth J Goldsmith et al. Chem Rev. 2007 Nov.
No abstract available

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Figures

Figure 1
Figure 1
a) Secondary structure of protein kinases based on PKA. Helices are cyan, β-strands magenta, and loops deep salmon, b) The MAP kinase docking groove, the AGC hydrophobic motif (HM) pocket, and CDK2 recruitment peptide docking groove and SR docking groove are in violet. The cyclin-A binding site on CDK2 is in gray. Figures generated using PyMOL (Delano Scientific, San Carlos. CA).
Figure 2
Figure 2
The P+1 specificity pocket of Ser/Thr protein kinases a). All atom stereoview of the P+1 specificity pocket of PKA (PDB file 1ATP), carbon in green, oxygen in red, nitrogen in blue, phosphorus in orange and sulfur in yellow, b) P+1 specificity pocket of PKA (PDB file 1ATP), c) PHK (2PHK), d) CDK2 (1QMZ), e) ERK2 (2ERK), and f) CK1 (1CSN). In Figures 2b–2f, carbon atoms of the bound peptide are light blue, the P+1 pocket and APE helix are yellow, the activation segment is green, the catalytic loop is magenta, and helix G is cyan. In Figures 2b–2f only the P+1 pocket, close by catalytic residues, and the activation segment phosphorylation site are shown rendered in ball-and-stick representation. Hydrogen bonds are shown in red dashed lines.
Figure 2
Figure 2
The P+1 specificity pocket of Ser/Thr protein kinases a). All atom stereoview of the P+1 specificity pocket of PKA (PDB file 1ATP), carbon in green, oxygen in red, nitrogen in blue, phosphorus in orange and sulfur in yellow, b) P+1 specificity pocket of PKA (PDB file 1ATP), c) PHK (2PHK), d) CDK2 (1QMZ), e) ERK2 (2ERK), and f) CK1 (1CSN). In Figures 2b–2f, carbon atoms of the bound peptide are light blue, the P+1 pocket and APE helix are yellow, the activation segment is green, the catalytic loop is magenta, and helix G is cyan. In Figures 2b–2f only the P+1 pocket, close by catalytic residues, and the activation segment phosphorylation site are shown rendered in ball-and-stick representation. Hydrogen bonds are shown in red dashed lines.
Figure 3
Figure 3
Docking interactions between kinase and corresponding peptides with the kinase surface rendered in gray, otherwise the coloring scheme is the same as in Figure 1. a) ERK2 and docking peptide HePTP (2GPH). Carbon atoms of the peptide are blue. Note how the peptide helix orients the Arg20’ and Arg21’ toward the ERK2 acidic patch. b) PKA (1ATP). C-terminus of PKA in blue binds in the kinase HM pocket. Note how the reverse turn (at Thr348-Glu349) brings Phe347 and Phe35O close together. The side-chain of Thr348, which caps the helical turn, has been eliminated for clarity, c) CDK2 with recruitment peptide pi07 (1H28). Peptide, shown in blue, is bound in the hydrophobic crevice formed by kinase helices 1 and 3. d) Surface representation of pCDK2/cyclin-A with CDC6 bis-substrate inhibitor spanning active site and recruitment site. Visible residues shown in stick representation; disordered residues indicated by green balls. e) SRPK1 with docking peptide ASF/SF2 in blue (1WBP) showing arginine-mediated interactions.
Figure 3
Figure 3
Docking interactions between kinase and corresponding peptides with the kinase surface rendered in gray, otherwise the coloring scheme is the same as in Figure 1. a) ERK2 and docking peptide HePTP (2GPH). Carbon atoms of the peptide are blue. Note how the peptide helix orients the Arg20’ and Arg21’ toward the ERK2 acidic patch. b) PKA (1ATP). C-terminus of PKA in blue binds in the kinase HM pocket. Note how the reverse turn (at Thr348-Glu349) brings Phe347 and Phe35O close together. The side-chain of Thr348, which caps the helical turn, has been eliminated for clarity, c) CDK2 with recruitment peptide pi07 (1H28). Peptide, shown in blue, is bound in the hydrophobic crevice formed by kinase helices 1 and 3. d) Surface representation of pCDK2/cyclin-A with CDC6 bis-substrate inhibitor spanning active site and recruitment site. Visible residues shown in stick representation; disordered residues indicated by green balls. e) SRPK1 with docking peptide ASF/SF2 in blue (1WBP) showing arginine-mediated interactions.
Figure 4
Figure 4
Peptide induced allostery in MAP kinases and AGC kinases. a) ERK2/pepHePTP (2GPH) superimposed with unphosphorylated unliganded ERK2 (1ERK). Note the very large changes in the activation segment, and changes in the N-terminus. b) PKB/GSK3 peptide (1O6K) superimposed with unphosphorylated PKB (1MRY). Helices B and C, as well as the activation segment become ordered in peptide-bound PKB. Unliganded conformations are rendered in cyan, and activation segment green. Peptide-bound structures are pink, activation segment red, and peptide yellow.
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