The active conformation of the PAK1 kinase domain. Export

@article{Lei2005, abstract = {The p21-activated kinases (PAKs) participate in cytoskeletal control networks, downstream of Rho-family GTPases. A structure of PAK1 in an autoregulated, "off" state showed that a regulatory region, N-terminal to the kinase domain, forces the latter into an inactive conformation, prevents phosphorylation of Thr423 in the activation loop, and promotes dimerization. We have now determined structures at 1.8 A resolution for the free PAK1 kinase domain, with a mutation in the active site that blocks enzymatic activity, and for the same domain with a "phosphomimetic" mutation in the activation loop. The two very similar structures show that even in the absence of a phosphorylated Thr423, the kinase has an essentially active conformation. When Cdc42 binds the regulatory region and dissociates the dimer, PAK1 will be in an "intermediate-active" state, with a capacity to phosphorylate itself or other substrates even prior to modification of its activation loop.}, author = {Lei, Ming and Robinson, Michael A. and Harrison, Stephen C.}, citeulike-article-id = {2054442}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.str.2005.03.007}, doi = {10.1016/j.str.2005.03.007}, journal = {Structure}, keywords = {adenosine, article-predikin, binding, data, diffraction, human, kinase, molecular, mutation, protein, protein-serine-threonine, sequence, sites, structure, tertiary, triphosphate, x-ray}, month = {May}, number = {5}, pages = {769--778}, posted-at = {2007-12-04 03:22:13}, priority = {2}, title = {The active conformation of the PAK1 kinase domain.}, url = {10.1016/j.str.2005.03.007}, volume = {13}, year = {2005} }

TY - JOUR ID - Lei2005 L3 - citeulike-article-id:2054442 N2 - The p21-activated kinases (PAKs) participate in cytoskeletal control networks, downstream of Rho-family GTPases. A structure of PAK1 in an autoregulated, "off" state showed that a regulatory region, N-terminal to the kinase domain, forces the latter into an inactive conformation, prevents phosphorylation of Thr423 in the activation loop, and promotes dimerization. We have now determined structures at 1.8 A resolution for the free PAK1 kinase domain, with a mutation in the active site that blocks enzymatic activity, and for the same domain with a "phosphomimetic" mutation in the activation loop. The two very similar structures show that even in the absence of a phosphorylated Thr423, the kinase has an essentially active conformation. When Cdc42 binds the regulatory region and dissociates the dimer, PAK1 will be in an "intermediate-active" state, with a capacity to phosphorylate itself or other substrates even prior to modification of its activation loop. IS - 5 JF - Structure EP - 778 TI - The active conformation of the PAK1 kinase domain. VL - 13 SP - 769 KW - adenosine KW - article-predikin KW - binding KW - data KW - diffraction KW - human KW - kinase KW - molecular KW - mutation KW - protein KW - protein-serine-threonine KW - sequence KW - sites KW - structure KW - tertiary KW - triphosphate KW - x-ray AU - Lei, Ming AU - Robinson, Michael AU - Harrison, Stephen PY - 2005/May// UR - http://dx.doi.org/10.1016/j.str.2005.03.007 ER -