3DLS

Crystal structure of human PAS kinase bound to ADP

3DLS の概要

• エントリーDOI: 10.2210/pdb3dls/pdb
• 分子名称: PAS domain-containing serine/threonine-protein kinase, MAGNESIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: pas kinase, pask, protein kinase, drug discovery, atp-binding, kinase, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase, structural genomics, psi-2, protein structure initiative, new york sgx research center for structural genomics, nysgxrc
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 230276.62

構造登録者

Antonysamy, S.,Bonanno, J.B.,Romero, R.,Russell, M.,Iizuka, M.,Gheyi, T.,Wasserman, S.R.,Rutter, J.,Sauder, J.M.,Burley, S.K.,New York SGX Research Center for Structural Genomics (NYSGXRC) (登録日: 2008-06-29, 公開日: 2008-08-26, 最終更新日: 2024-02-21)

主引用文献

Kikani, C.K.,Antonysamy, S.A.,Bonanno, J.B.,Romero, R.,Zhang, F.F.,Russell, M.,Gheyi, T.,Iizuka, M.,Emtage, S.,Sauder, J.M.,Turk, B.E.,Burley, S.K.,Rutter, J.
Structural bases of PAS domain-regulated kinase (PASK) activation in the absence of activation loop phosphorylation.
J.Biol.Chem., 285:41034-41043, 2010

PubMed Abstract: Per-Arnt-Sim (PAS) domain-containing protein kinase (PASK) is an evolutionary conserved protein kinase that coordinates cellular metabolism with metabolic demand in yeast and mammals. The molecular mechanisms underlying PASK regulation, however, remain unknown. Herein, we describe a crystal structure of the kinase domain of human PASK, which provides insights into the regulatory mechanisms governing catalysis. We show that the kinase domain adopts an active conformation and has catalytic activity in vivo and in vitro in the absence of activation loop phosphorylation. Using site-directed mutagenesis and structural comparison with active and inactive kinases, we identified several key structural features in PASK that enable activation loop phosphorylation-independent activity. Finally, we used combinatorial peptide library screening to determine that PASK prefers basic residues at the P-3 and P-5 positions in substrate peptides. Our results describe the key features of the PASK structure and how those features are important for PASK activity and substrate selection.

PubMed: 20943661
DOI: 10.1074/jbc.M110.157594

実験手法

X-RAY DIFFRACTION (2.3 Å)