3AGM

Complex of PKA with the bisubstrate protein kinase inhibitor ARC-670

3AGM の概要

• エントリーDOI: 10.2210/pdb3agm/pdb
• 関連するPDBエントリー: 3BWJ 3ag9 3agl
• 関連するBIRD辞書のPRD_ID: PRD_001021
• 分子名称: cAMP-dependent protein kinase catalytic subunit alpha, N~2~-{8-OXO-8-[4-(9H-PURIN-6-YL)PIPERAZIN-1-YL]OCTANOYL}-D-ARGINYL-D-ARGINYL-D-ARGINYL-D-ARGINYL-D-ARGINYL-D-ARGININAMIDE (3 entities in total)
• 機能のキーワード: pka, protein kinase a, bisubstrate, bisubstrate inhibitor, arc-670, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P17612
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42110.15

構造登録者

Pflug, A.,Ragozina, J.,Uri, A.,Bossemeyer, D.,Engh, R.A. (登録日: 2010-04-02, 公開日: 2010-09-01, 最終更新日: 2024-11-13)

主引用文献

Pflug, A.,Rogozina, J.,Lavogina, D.,Enkvist, E.,Uri, A.,Engh, R.A.,Bossemeyer, D.
Diversity of bisubstrate binding modes of adenosine analogue-oligoarginine conjugates in protein kinase a and implications for protein substrate interactions.
J.Mol.Biol., 403:66-77, 2010

PubMed Abstract: Crystal structures of the catalytic subunit α of cAMP-dependent protein kinase (PKAc) with three adenosine analogue-oligoarginine conjugates (ARCs) are presented. The rationally designed ARCs include moieties that, in combination, target both the ATP- and the peptide-substrate-binding sites of PKAc, thereby taking advantage of high-affinity binding interactions offered by the ATP site while utilizing an additional mechanism for target specificity via binding to the peptide substrate site. The crystal structures demonstrate that, in accord with the previously reported bisubstrate character of ARCs, the inhibitors occupy both binding sites of PKAc. Further, they show new binding modes that may also apply to natural protein substrates of PKAc, which have not been revealed by previous crystallographic studies. The crystal structures described here contribute to the understanding of the substrate-binding patterns of PKAc and should also facilitate the design of inhibitors targeting PKAc and related protein kinases.

PubMed: 20732331
DOI: 10.1016/j.jmb.2010.08.028

実験手法

X-RAY DIFFRACTION (2 Å)