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6WLX

PAK4 kinase domain in complex with beta-catenin Ser675 substrate peptide

Summary for 6WLX
Entry DOI10.2210/pdb6wlx/pdb
DescriptorSerine/threonine-protein kinase PAK 4, Catenin beta-1 (3 entities in total)
Functional Keywordsserine/threonine kinase pak4, beta-catenin, phosphopeptide, ser675, transferase
Biological sourceHomo sapiens (Human)
More
Total number of polymer chains2
Total formula weight39985.18
Authors
Chetty, A.K.,Ha, B.H.,Boggon, T.J. (deposition date: 2020-04-20, release date: 2020-06-24, Last modification date: 2024-10-30)
Primary citationChetty, A.K.,Sexton, J.A.,Ha, B.H.,Turk, B.E.,Boggon, T.J.
Recognition of physiological phosphorylation sites by p21-activated kinase 4.
J.Struct.Biol., 211:107553-107553, 2020
Cited by
PubMed Abstract: Many serine/threonine protein kinases discriminate between serine and threonine substrates as a filter to control signaling output. Among these, the p21-activated kinase (PAK) group strongly favors phosphorylation of Ser over Thr residues. PAK4, a group II PAK, almost exclusively phosphorylates its substrates on serine residues. The only well documented exception is LIM domain kinase 1 (LIMK1), which is phosphorylated on an activation loop threonine (Thr508) to promote its catalytic activity. To understand the molecular and kinetic basis for PAK4 substrate selectivity we compared its mode of recognition of LIMK1 (Thr508) with that of a known serine substrate, β-catenin (Ser675). We determined X-ray crystal structures of PAK4 in complex with synthetic peptides corresponding to its phosphorylation sites in LIMK1 and β-catenin to 1.9 Å and 2.2 Å resolution, respectively. We found that the PAK4 DFG + 1 residue, a key determinant of phosphoacceptor preference, adopts a sub-optimal orientation when bound to LIMK1 compared to β-catenin. In peptide kinase activity assays, we find that phosphoacceptor identity impacts catalytic efficiency but does not affect the K value for both phosphorylation sites. Although catalytic efficiency of wild-type LIMK1 and β-catenin are equivalent, T508S mutation of LIMK1 creates a highly efficient substrate. These results suggest suboptimal phosphorylation of LIMK1 as a mechanism for controlling the dynamics of substrate phosphorylation by PAK4.
PubMed: 32585314
DOI: 10.1016/j.jsb.2020.107553
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.2 Å)
Structure validation

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數據於2025-07-16公開中

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