PMID:22153498

Citation	Wang, J, Wu, JW and Wang, ZX (2011) Structural insights into the autoactivation mechanism of p21-activated protein kinase. Structure 19:1752-61
Abstract	p21-activated kinases (PAKs) play an important role in diverse cellular processes. Full activation of PAKs requires autophosphorylation of a critical threonine/serine located in the activation loop of the kinase domain. Here we report crystal structures of the phosphorylated and unphosphorylated PAK1 kinase domain. The phosphorylated PAK1 kinase domain has a conformation typical of all active protein kinases. Interestingly, the structure of the unphosphorylated PAK1 kinase domain reveals an unusual dimeric arrangement expected in an authentic enzyme-substrate complex, in which the activation loop of the putative "substrate" is projected into the active site of the "enzyme." The enzyme is bound to AMP-PNP and has an active conformation, whereas the substrate is empty and adopts an inactive conformation. Thus, the structure of the asymmetric homodimer mimics a trans-autophosphorylation complex, and suggests that unphosphorylated PAK1 could dynamically adopt both the active and inactive conformations in solution.
Links	PubMed Online version:10.1016/j.str.2011.10.013
Keywords	Binding Sites; Humans; Kinetics; Models, Molecular; Phosphorylation; Protein Conformation; Structure-Activity Relationship; p21-Activated Kinases/chemistry; p21-Activated Kinases/metabolism
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Significance

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:PAK1	enables	GO:0042802: identical protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q13153-1	F		Seeded From UniProt	complete

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