3DLS

Crystal structure of human PAS kinase bound to ADP

Summary for 3DLS

• Entry DOI: 10.2210/pdb3dls/pdb
• Descriptor: PAS domain-containing serine/threonine-protein kinase, MAGNESIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: 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
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 6
• Total formula weight: 230276.62

Authors

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) (deposition date: 2008-06-29, release date: 2008-08-26, Last modification date: 2024-02-21)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.3 Å)