4fig | pdb_00004fig

Catalytic domain of human PAK4

spinqualitylabelsall models 4fig, resolution 3.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4fig is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ANP, MG NonStd Res: SEP Related: 4fie, 4fif, 4fih, 4fii, 4fij Gene: KIAA1142, PAK4 (Homo sapiens) Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed The type II p21-activated kinases (PAKs) are key effectors of RHO-family GTPases involved in cell motility, survival, and proliferation. Using a structure-guided approach, we discovered that type II PAKs are regulated by an N-terminal autoinhibitory pseudosubstrate motif centered on a critical proline residue, and that this regulation occurs independently of activation loop phosphorylation. We determined six X-ray crystal structures of either full-length PAK4 or its catalytic domain, that demonstrate the molecular basis for pseudosubstrate binding to the active state with phosphorylated activation loop. We show that full-length PAK4 is constitutively autoinhibited, but mutation of the pseudosubstrate releases this inhibition and causes increased phosphorylation of the apoptotic regulation protein Bcl-2/Bcl-X(L) antagonist causing cell death and cellular morphological changes. We also find that PAK6 is regulated by the pseudosubstrate region, indicating a common type II PAK autoregulatory mechanism. Finally, we find Src SH3, but not beta-PIX SH3, can activate PAK4. We provide a unique understanding for type II PAK regulation. Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory pseudosubstrate.,Ha BH, Davis MJ, Chen C, Lou HJ, Gao J, Zhang R, Krauthammer M, Halaban R, Schlessinger J, Turk BE, Boggon TJ Proc Natl Acad Sci U S A. 2012 Sep 17. PMID:22988085 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine/threonine protein kinase

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