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3dls

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Revision as of 22:37, 25 December 2014

Crystal structure of human PAS kinase bound to ADP

Structural highlights

3dls is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	PASK, KIAA0135 (Homo sapiens)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, RCSB, PDBsum, TOPSAN

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 PubMed

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.

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

↑ Wilson WA, Skurat AV, Probst B, de Paoli-Roach A, Roach PJ, Rutter J. Control of mammalian glycogen synthase by PAS kinase. Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16596-601. Epub 2005 Nov 7. PMID:16275910 doi:10.1073/pnas.0508481102
↑ An R, da Silva Xavier G, Hao HX, Semplici F, Rutter J, Rutter GA. Regulation by Per-Arnt-Sim (PAS) kinase of pancreatic duodenal homeobox-1 nuclear import in pancreatic beta-cells. Biochem Soc Trans. 2006 Nov;34(Pt 5):791-3. PMID:17052199 doi:10.1042/BST0340791
↑ Eckhardt K, Troger J, Reissmann J, Katschinski DM, Wagner KF, Stengel P, Paasch U, Hunziker P, Borter E, Barth S, Schlafli P, Spielmann P, Stiehl DP, Camenisch G, Wenger RH. Male germ cell expression of the PAS domain kinase PASKIN and its novel target eukaryotic translation elongation factor eEF1A1. Cell Physiol Biochem. 2007;20(1-4):227-40. PMID:17595531 doi:10.1159/000104169
↑ da Silva Xavier G, Farhan H, Kim H, Caxaria S, Johnson P, Hughes S, Bugliani M, Marselli L, Marchetti P, Birzele F, Sun G, Scharfmann R, Rutter J, Siniakowicz K, Weir G, Parker H, Reimann F, Gribble FM, Rutter GA. Per-arnt-sim (PAS) domain-containing protein kinase is downregulated in human islets in type 2 diabetes and regulates glucagon secretion. Diabetologia. 2011 Apr;54(4):819-27. doi: 10.1007/s00125-010-2010-7. Epub 2010, Dec 23. PMID:21181396 doi:10.1007/s00125-010-2010-7
↑ Schlafli P, Troger J, Eckhardt K, Borter E, Spielmann P, Wenger RH. Substrate preference and phosphatidylinositol monophosphate inhibition of the catalytic domain of the Per-Arnt-Sim domain kinase PASKIN. FEBS J. 2011 May;278(10):1757-68. doi: 10.1111/j.1742-4658.2011.08100.x. Epub, 2011 Apr 8. PMID:21418524 doi:10.1111/j.1742-4658.2011.08100.x
↑ 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. Structural bases of PAS domain-regulated kinase (PASK) activation in the absence of activation loop phosphorylation. J Biol Chem. 2010 Dec 24;285(52):41034-43. Epub 2010 Oct 13. PMID:20943661 doi:10.1074/jbc.M110.157594
↑ 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. Structural bases of PAS domain-regulated kinase (PASK) activation in the absence of activation loop phosphorylation. J Biol Chem. 2010 Dec 24;285(52):41034-43. Epub 2010 Oct 13. PMID:20943661 doi:10.1074/jbc.M110.157594

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3dls"

@@ Line 8: / Line 8: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dls FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dls OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3dls RCSB], [http://www.ebi.ac.uk/pdbsum/3dls PDBsum], [http://www.topsan.org/Proteins/NYSGXRC/3dls TOPSAN]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/PASK_HUMAN 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.<ref>PMID:16275910</ref> <ref>PMID:17052199</ref> <ref>PMID:17595531</ref> <ref>PMID:21181396</ref> <ref>PMID:21418524</ref> <ref>PMID:20943661</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3dls

From Proteopedia

Revision as of 22:37, 25 December 2014

Crystal structure of human PAS kinase bound to ADP

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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