4CT2

Human PDK1-PKCzeta Kinase Chimera

Summary for 4CT2

• Entry DOI: 10.2210/pdb4ct2/pdb
• Related: 4CT1
• Descriptor: 3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE 1, ADENOSINE-5'-TRIPHOSPHATE, DITHIANE DIOL, ... (5 entities in total)
• Functional Keywords: transferase, allosteric regulation, allosteric site, phosphorylation, agc protein kinase, chimeric protein
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: O15530
• Total number of polymer chains: 1
• Total formula weight: 36052.96

Authors

Schulze, J.O.,Zhang, H.,Lopez-Garcia, L.A.,Biondi, R.M. (deposition date: 2014-03-11, release date: 2014-05-28, Last modification date: 2023-12-20)

Primary citation

Zhang, H.,Neimanis, S.,Lopez-Garcia, L.A.,Arencibia, J.M.,Amon, S.,Stroba, A.,Zeuzem, S.,Proschak, E.,Stark, H.,Bauer, A.F.,Busschots, K.,Jorgensen, T.J.,Engel, M.,Schulze, J.O.,Biondi, R.M.
Molecular Mechanism of Regulation of the Atypical Protein Kinase C by N-Terminal Domains and an Allosteric Small Compound.
Chem.Biol., 21:754-, 2014

PubMed Abstract: Protein kinases play important regulatory roles in cells and organisms. Therefore, they are subject to specific and tight mechanisms of regulation that ultimately converge on the catalytic domain and allow the kinases to be activated or inhibited only upon the appropriate stimuli. AGC protein kinases have a pocket in the catalytic domain, the PDK1-interacting fragment (PIF)-pocket, which is a key mediator of the activation. We show here that helix αC within the PIF-pocket of atypical protein kinase C (aPKC) is the target of the interaction with its inhibitory N-terminal domains. We also provide structural evidence that the small compound PS315 is an allosteric inhibitor that binds to the PIF-pocket of aPKC. PS315 exploits the physiological dynamics of helix αC for its binding and allosteric inhibition. The results will support research on allosteric mechanisms and selective drug development efforts against PKC isoforms.

PubMed: 24836908
DOI: 10.1016/J.CHEMBIOL.2014.04.007

Experimental method

X-RAY DIFFRACTION (1.25 Å)