6FD3

Thiophosphorylated PAK3 kinase domain

Summary for 6FD3

• Entry DOI: 10.2210/pdb6fd3/pdb
• Descriptor: Serine/threonine-protein kinase PAK 3, MAGNESIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: kinase, thiophosphorylation, complex, adp, phosphorylated, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 34329.68

Authors

Sorrell, F.J.,Wang, D.,von Delft, F.,Bountra, C.,Edwards, A.M.,Elkins, J.M. (deposition date: 2017-12-21, release date: 2018-01-03, Last modification date: 2024-11-20)

Primary citation

Sorrell, F.J.,Kilian, L.M.,Elkins, J.M.
Solution structures and biophysical analysis of full-length group A PAKs reveal they are monomeric and auto-inhibited incis.
Biochem.J., 476:1037-1051, 2019

PubMed Abstract: The group A p21-activated kinases (PAKs) exist in an auto-inhibited form until activated by GTPase binding and auto-phosphorylation. In the auto-inhibited form, a regulatory domain binds to the kinase domain (KD) blocking the binding of substrates, and CDC42 or Rac binding to the regulatory domain relieves this auto-inhibition allowing auto-phosphorylation on the KD activation loop. We have determined the crystal structure of the PAK3 catalytic domain and by small angle X-ray scattering, the solution-phase structures of full-length inactive PAK1 and PAK3. The structures reveal a compact but elongated molecular shape that demonstrates that, together with multiple independent biophysical measurements and in contrast with previous assumptions, group A PAKs are monomeric both before and after activation, consistent with an activation mechanism of -auto-inhibition and initial -auto-phosphorylation, followed by transient dimerisation to allow -auto-phosphorylation for full activation, yielding a monomeric active PAK protein.

PubMed: 30858169
DOI: 10.1042/BCJ20180867

Experimental method

X-RAY DIFFRACTION (1.52 Å)