2J51: Crystal Structure Of Human Ste20-Like Kinase Bound To 5- Amino-3-((4-(Aminosulfonyl)phenyl)amino)-N-(2,6- Difluorophenyl)-1h-1,2,4-Triazole-1-Carbothioamide

Protein kinase autophosphorylation of activation segment residues is a common regulatory mechanism in phosphorylation-dependent signalling cascades. However, the molecular mechanisms that guarantee specific and efficient phosphorylation of these sites have not been elucidated. Here, we report on three novel and diverse protein kinase structures that reveal an exchanged activation segment conformation. This dimeric arrangement results in an active kinase conformation in trans, with activation segment phosphorylation sites in close proximity to the active site of the interacting protomer. Analytical ultracentrifugation and chemical cross-linking confirmed the presence of dimers in solution. Consensus substrate sequences for each kinase showed that the identified activation segment autophosphorylation sites are non-consensus substrate sites. Based on the presented structural and functional data, a model for specific activation segment phosphorylation at non-consensus substrate sites is proposed that is likely to be common to other kinases from diverse subfamilies.
PDB ID: 2J51Download
MMDB ID: 42492
PDB Deposition Date: 2006/9/8
Updated in MMDB: 2006/11
Experimental Method:
x-ray diffraction
Resolution: 2.1  Å
Source Organism:
Similar Structures:
Biological Unit for 2J51: dimeric; determined by author and by software (PQS)
Molecular Components in 2J51
Label Count Molecule
Proteins (2 molecules)
Ste20-like Serine/threonine-protein Kinase(Gene symbol: SLK)
Molecule annotation
Chemicals (12 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB