4CT1

Human PDK1-PKCzeta Kinase Chimera in Complex with Allosteric Compound PS315 Bound to the PIF-Pocket

4CT1 の概要

• エントリーDOI: 10.2210/pdb4ct1/pdb
• 関連するPDBエントリー: 4CT2
• 分子名称: 3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE 1, ADENOSINE-5'-TRIPHOSPHATE, (2Z)-3-(biphenyl-4-yl)-5-(4-chlorophenyl)pent-2-enoic acid, ... (6 entities in total)
• 機能のキーワード: transferase, allosteric regulation, allosteric site, phosphorylation, agc protein kinase, chimeric protein
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: O15530
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36470.96

構造登録者

Schulze, J.O.,Zhang, H.,Lopez-Garcia, L.A.,Biondi, R.M. (登録日: 2014-03-11, 公開日: 2014-05-28, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.85 Å)