Journal: Cellular Logistics

Article Title: 3D structure analysis of PAKs

doi: 10.4161/cl.21883

Figure Lengend Snippet: Figure 1. Exploring small molecule (ligand) binding sites in kinase domain from group I and group II PAKs. (A) PAK1 kinase domain (PDB ID: 3Q52 ) and (B) PAK4 kinase domain (PDB ID: 2J0I ) were evaluated for ligand binding sites (shown as “red” mesh) using Q-SiteFinder method. The figures were created using PyMOL.

Article Snippet: Recently a few potent PAK1-specific inhibitors (IC 50 ~10 nM) were developed by Afraxis; the IC 50 for PAK4-6 is poorer by 100-fold (~1 μM), suggesting that the target ATP-binding pocket of these two distinct kinases substantially differ from each other in atomic detail.

Techniques: Ligand Binding Assay

Journal: Cellular Logistics

Article Title: 3D structure analysis of PAKs

doi: 10.4161/cl.21883

Figure Lengend Snippet: Table 1. disEMBL prediction for ordered or disordered states of PAK1 residues 1-77 and PAK1 residues 148-248

Article Snippet: Recently a few potent PAK1-specific inhibitors (IC 50 ~10 nM) were developed by Afraxis; the IC 50 for PAK4-6 is poorer by 100-fold (~1 μM), suggesting that the target ATP-binding pocket of these two distinct kinases substantially differ from each other in atomic detail.

Techniques: Sequencing

Journal: Cellular Logistics

Article Title: 3D structure analysis of PAKs

doi: 10.4161/cl.21883

Figure Lengend Snippet: Figure 2. Conformational representation of PAK peptides known to interact with other proteins. (A) Aligned CRIB domains from PAK1 (green) and PAK6 (magenta) that interact with CDC42 (PDB ID: 1E0A and 2ODB ). (B) Aligned CRIB domains from PAK1 (green) and PAK4 (magenta) that interact with Rac3 (PDB ID: 2QME and 2OV2 ). (C) Aligned β-PIX binding regions from PAK1 (green) and PAK2 (magenta) (PDB ID: 1ZSG and 2DF6 ). (D) LC8 interacting peptide from PAK1 (PDB ID: 3DVP ). Stabilized analogs of these peptides, which are pre-formed in the bound-state conformation, can block the interactions between PAKs and the partner proteins.

Article Snippet: Recently a few potent PAK1-specific inhibitors (IC 50 ~10 nM) were developed by Afraxis; the IC 50 for PAK4-6 is poorer by 100-fold (~1 μM), suggesting that the target ATP-binding pocket of these two distinct kinases substantially differ from each other in atomic detail.

Techniques: Binding Assay, Blocking Assay

Journal: Cellular Logistics

Article Title: 3D structure analysis of PAKs

doi: 10.4161/cl.21883

Figure Lengend Snippet: Figure 3. Native (ATP) and non-native (inhibitors) molecules bound in the active site of PAK1 kinase domain. (A) Structural alignment of PDB IDs 3Q53 (green), 3FXZ (cyan), 3FY0 (magenta) and 2HY8 (yellow). (B) Magnified active site showing ATP (green sticks) and inhibitors (spheres in cyan, magenta and yellow). Depending on the molecule bound in the active site, strands β1, β2 and the loop connecting them show movements either away or toward the C-lobe of the kinase domain.

Article Snippet: Recently a few potent PAK1-specific inhibitors (IC 50 ~10 nM) were developed by Afraxis; the IC 50 for PAK4-6 is poorer by 100-fold (~1 μM), suggesting that the target ATP-binding pocket of these two distinct kinases substantially differ from each other in atomic detail.

Techniques:

Journal: Cellular Logistics

Article Title: 3D structure analysis of PAKs

doi: 10.4161/cl.21883

Figure Lengend Snippet: Figure 5. A de novo method for designing a novel affinity reagent for PAK1. (A) A scaffold protein (cyan) is randomly docked at the selected hotspot site between helices αEF and αG of PAK1 kinase domain (yellow). This step is required for searching through conformational space for adequate shape complementarity. A truncated kinase domain is shown here for clarity. (B) An energetically good docked conformation is designed on the scaffold side for maximal interaction with the kinase domain. A representative design, Spider Roll is shown here with the residues involved in protein-protein interaction shown as sticks. This figure is reprinted from Jha et al. with permission from Elsevier.

Article Snippet: Recently a few potent PAK1-specific inhibitors (IC 50 ~10 nM) were developed by Afraxis; the IC 50 for PAK4-6 is poorer by 100-fold (~1 μM), suggesting that the target ATP-binding pocket of these two distinct kinases substantially differ from each other in atomic detail.

Techniques: