5J0A

Crystal structure of PDZ-binding kinase

Summary for 5J0A

• Entry DOI: 10.2210/pdb5j0a/pdb
• Descriptor: Lymphokine-activated killer T-cell-originated protein kinase, SULFATE ION, 4'-HYDROXYCINNAMIC ACID, ... (5 entities in total)
• Functional Keywords: protein kinase, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 69247.77

Authors

Zou, Q.W.,Zhou, H.,Yang, X. (deposition date: 2016-03-28, release date: 2016-09-07, Last modification date: 2024-03-20)

Primary citation

Dong, C.,Tang, X.,Xie, Y.,Zou, Q.,Yang, X.,Zhou, H.
The crystal structure of an inactive dimer of PDZ-binding kinase
Biochem.Biophys.Res.Commun., 476:586-593, 2016

PubMed Abstract: The overexpression of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) has been associated with hematologic tumors, breast cancer and various other cancers. However, the three-dimensional structure of PBK has not been solved. In this study, we determined the crystal structure of human PBK, which has two phospho-mimicking mutations T9E and T198E. The structural data indicated that PBK may assemble into an inactive dimer in alkaline conditions. Analytical size-exclusion chromatography and analytical ultracentrifugation confirmed that PBK exists in a conformational transition between dimers and monomers at different pH conditions. Co-IP and kinase assays suggested that the active state of PBK is a monomer and does not form a dimer even under alkaline conditions. These results showed that the conformational transition of PBK is important for its kinase activity regulation. Collectively, our observations may provide a novel starting point for structure-based functional studies.

PubMed: 27262437
DOI: 10.1016/j.bbrc.2016.05.166

Experimental method

X-RAY DIFFRACTION (2.74 Å)