4JDJ: Crystal Structure Of Serine/threonine-protein Kinase Pak 4 F461v Mutant In Complex With Paktide T Peptide Substrate

Eukaryotic protein kinases are generally classified as being either tyrosine or serine-threonine specific. Though not evident from inspection of their primary sequences, many serine-threonine kinases display a significant preference for serine or threonine as the phosphoacceptor residue. Here we show that a residue located in the kinase activation segment, which we term the "DFG+1" residue, acts as a major determinant for serine-threonine phosphorylation site specificity. Mutation of this residue was sufficient to switch the phosphorylation site preference for multiple kinases, including the serine-specific kinase PAK4 and the threonine-specific kinase MST4. Kinetic analysis of peptide substrate phosphorylation and crystal structures of PAK4-peptide complexes suggested that phosphoacceptor residue preference is not mediated by stronger binding of the favored substrate. Rather, favored kinase-phosphoacceptor combinations likely promote a conformation optimal for catalysis. Understanding the rules governing kinase phosphoacceptor preference allows kinases to be classified as serine or threonine specific based on their sequence.
PDB ID: 4JDJDownload
MMDB ID: 117028
PDB Deposition Date: 2013/2/25
Updated in MMDB: 2014/01
Experimental Method:
x-ray diffraction
Resolution: 2.3  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4JDJ: dimeric; determined by author and by software (PISA)
Molecular Components in 4JDJ
Label Count Molecule
Proteins (2 molecules)
Serine/threonine-protein Kinase PAK 4(Gene symbol: PAK4)
Molecule annotation
Paktide T
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB