3dls
From Proteopedia
Crystal structure of human PAS kinase bound to ADP
Structural highlights
Function[PASK_HUMAN] Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate to respiratory regulation.[1] [2] [3] [4] [5] [6] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPer-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. Structural bases of PAS domain-regulated kinase (PASK) activation in the absence of activation loop phosphorylation.,Kikani CK, Antonysamy SA, Bonanno JB, Romero R, Zhang FF, Russell M, Gheyi T, Iizuka M, Emtage S, Sauder JM, Turk BE, Burley SK, Rutter J J Biol Chem. 2010 Dec 24;285(52):41034-43. Epub 2010 Oct 13. PMID:20943661[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Non-specific serine/threonine protein kinase | Antonysamy, S | Bonanno, J B | Burley, S K | Gheyi, T | Iizuka, M | Structural genomic | Romero, R | Russell, M | Rutter, J | Sauder, J M | Wasserman, S R | Atp-binding | Drug discovery | Kinase | Nucleotide-binding | NYSGXRC, New York SGX Research Center for Structural Genomics | Pas kinase | Pask | Phosphoprotein | Protein kinase | PSI, Protein structure initiative | Serine/threonine-protein kinase | Transferase
