3O7L

Crystal Structure of phospholamban (1-19):PKA C-subunit:AMP-PNP:Mg2+ complex

3O7L の概要

• エントリーDOI: 10.2210/pdb3o7l/pdb
• 関連するPDBエントリー: 1ATP
• 分子名称: cAMP-dependent protein kinase catalytic subunit alpha, Cardiac phospholamban, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: protein kinase a, phospholamban, allostery, substrate recognition, conformational selection, intrinsically disordered proteins, membrane proteins, transferase
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Cytoplasm (By similarity): P05132 P05132; Mitochondrion membrane; Single-pass membrane protein: P61014
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 83633.60

構造登録者

Cheng, C.Y.,Taylor, S.S. (登録日: 2010-07-30, 公開日: 2010-10-06, 最終更新日: 2024-10-16)

主引用文献

Masterson, L.R.,Cheng, C.,Yu, T.,Tonelli, M.,Kornev, A.,Taylor, S.S.,Veglia, G.
Dynamics connect substrate recognition to catalysis in protein kinase A.
Nat.Chem.Biol., 6:821-828, 2010

PubMed Abstract: Atomic resolution studies of protein kinases have traditionally been carried out in the inhibitory state, limiting our current knowledge on the mechanisms of substrate recognition and catalysis. Using NMR, X-ray crystallography and thermodynamic measurements, we analyzed the substrate recognition process of cAMP-dependent protein kinase (PKA), finding that entropy and protein dynamics play a prominent role. The nucleotide acts as a dynamic and allosteric activator by coupling the two lobes of apo PKA, enhancing the enzyme dynamics synchronously and priming it for catalysis. The formation of the ternary complex is entropically driven, and NMR spin relaxation data reveal that both substrate and PKA are dynamic in the closed state. Our results show that the enzyme toggles between open and closed states, which indicates that a conformational selection rather than an induced-fit mechanism governs substrate recognition.

PubMed: 20890288
DOI: 10.1038/nchembio.452

実験手法

X-RAY DIFFRACTION (2.8 Å)