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3a8x

From Proteopedia

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Crystal Structure of PKCiota kinase domain

Structural highlights

3a8x is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	3a8w
Activity:	Protein kinase C, with EC number 2.7.11.13
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[KPCI_HUMAN] Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14]

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

Protein kinase C (PKC) plays an essential role in a wide range of cellular functions. Although crystal structures of the PKC-theta, PKC-iota and PKC-betaII kinase domains have previously been determined in complexes with small-molecule inhibitors, no structure of a PKC-substrate complex has been determined. In the previously determined PKC-iota complex, residues 533-551 in the C-terminal tail were disordered. In the present study, crystal structures of the PKC-iota kinase domain in its ATP-bound and apo forms were determined at 2.1 and 2.0 A resolution, respectively. In the ATP complex, the electron density of all of the C-terminal tail residues was well defined. In the structure, the side chain of Phe543 protrudes into the ATP-binding pocket to make van der Waals interactions with the adenine moiety of ATP; this is also observed in other AGC kinase structures such as binary and ternary substrate complexes of PKA and AKT. In addition to this interaction, the newly defined residues around the turn motif make multiple hydrogen bonds to glycine-rich-loop residues. These interactions reduce the flexibility of the glycine-rich loop, which is organized for ATP binding, and the resulting structure promotes an ATP conformation that is suitable for the subsequent phosphoryl transfer. In the case of the apo form, the structure and interaction mode of the C-terminal tail of PKC-iota are essentially identical to those of the ATP complex. These results indicate that the protein structure is pre-organized before substrate binding to PKC-iota, which is different from the case of the prototypical AGC-branch kinase PKA.

Structures of the PKC-iota kinase domain in its ATP-bound and apo forms reveal defined structures of residues 533-551 in the C-terminal tail and their roles in ATP binding.,Takimura T, Kamata K, Fukasawa K, Ohsawa H, Komatani H, Yoshizumi T, Takahashi I, Kotani H, Iwasawa Y Acta Crystallogr D Biol Crystallogr. 2010 May;66(Pt 5):577-83. Epub 2010 Apr 21. PMID:20445233^[15]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Selbie LA, Schmitz-Peiffer C, Sheng Y, Biden TJ. Molecular cloning and characterization of PKC iota, an atypical isoform of protein kinase C derived from insulin-secreting cells. J Biol Chem. 1993 Nov 15;268(32):24296-302. PMID:8226978
↑ Murray NR, Fields AP. Atypical protein kinase C iota protects human leukemia cells against drug-induced apoptosis. J Biol Chem. 1997 Oct 31;272(44):27521-4. PMID:9346882
↑ Wooten MW, Seibenhener ML, Zhou G, Vandenplas ML, Tan TH. Overexpression of atypical PKC in PC12 cells enhances NGF-responsiveness and survival through an NF-kappaB dependent pathway. Cell Death Differ. 1999 Aug;6(8):753-64. PMID:10467349 doi:10.1038/sj.cdd.4400548
↑ Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J. The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation. EMBO J. 1999 Jun 1;18(11):3044-53. PMID:10356400 doi:10.1093/emboj/18.11.3044
↑ Spitaler M, Villunger A, Grunicke H, Uberall F. Unique structural and functional properties of the ATP-binding domain of atypical protein kinase C-iota. J Biol Chem. 2000 Oct 27;275(43):33289-96. PMID:10906326 doi:10.1074/jbc.M002742200
↑ Xie J, Guo Q, Zhu H, Wooten MW, Mattson MP. Protein kinase C iota protects neural cells against apoptosis induced by amyloid beta-peptide. Brain Res Mol Brain Res. 2000 Oct 20;82(1-2):107-13. PMID:11042363
↑ Tisdale EJ. Glyceraldehyde-3-phosphate dehydrogenase is phosphorylated by protein kinase Ciota /lambda and plays a role in microtubule dynamics in the early secretory pathway. J Biol Chem. 2002 Feb 1;277(5):3334-41. Epub 2001 Nov 27. PMID:11724794 doi:10.1074/jbc.M109744200
↑ Tisdale EJ, Wang J, Silver RB, Artalejo CR. Atypical protein kinase C plays a critical role in protein transport from pre-Golgi intermediates. J Biol Chem. 2003 Sep 26;278(39):38015-21. Epub 2003 Jul 17. PMID:12871960 doi:10.1074/jbc.M305381200
↑ Mamidipudi V, Lin C, Seibenhener ML, Wooten MW. Regulation of interleukin receptor-associated kinase (IRAK) phosphorylation and signaling by iota protein kinase C. J Biol Chem. 2004 Feb 6;279(6):4161-5. Epub 2003 Dec 18. PMID:14684752 doi:10.1074/jbc.C300431200
↑ Regala RP, Weems C, Jamieson L, Copland JA, Thompson EA, Fields AP. Atypical protein kinase Ciota plays a critical role in human lung cancer cell growth and tumorigenicity. J Biol Chem. 2005 Sep 2;280(35):31109-15. Epub 2005 Jul 1. PMID:15994303 doi:M505402200
↑ Wald FA, Oriolo AS, Mashukova A, Fregien NL, Langshaw AH, Salas PJ. Atypical protein kinase C (iota) activates ezrin in the apical domain of intestinal epithelial cells. J Cell Sci. 2008 Mar 1;121(Pt 5):644-54. doi: 10.1242/jcs.016246. Epub 2008 Feb, 12. PMID:18270268 doi:10.1242/jcs.016246
↑ Staiger K, Schatz U, Staiger H, Weyrich P, Haas C, Guirguis A, Machicao F, Haring HU, Kellerer M. Protein kinase C iota mediates lipid-induced apoptosis of human coronary artery endothelial cells. Microvasc Res. 2009 Jun;78(1):40-4. doi: 10.1016/j.mvr.2009.01.014. Epub 2009 Mar, 25. PMID:19327373 doi:10.1016/j.mvr.2009.01.014
↑ Desai S, Pillai P, Win-Piazza H, Acevedo-Duncan M. PKC-iota promotes glioblastoma cell survival by phosphorylating and inhibiting BAD through a phosphatidylinositol 3-kinase pathway. Biochim Biophys Acta. 2011 Jun;1813(6):1190-7. doi: 10.1016/j.bbamcr.2011.03.007., Epub 2011 Mar 17. PMID:21419810 doi:10.1016/j.bbamcr.2011.03.007
↑ Justilien V, Jameison L, Der CJ, Rossman KL, Fields AP. Oncogenic activity of Ect2 is regulated through protein kinase C iota-mediated phosphorylation. J Biol Chem. 2011 Mar 11;286(10):8149-57. doi: 10.1074/jbc.M110.196113. Epub 2010, Dec 28. PMID:21189248 doi:10.1074/jbc.M110.196113
↑ Takimura T, Kamata K, Fukasawa K, Ohsawa H, Komatani H, Yoshizumi T, Takahashi I, Kotani H, Iwasawa Y. Structures of the PKC-iota kinase domain in its ATP-bound and apo forms reveal defined structures of residues 533-551 in the C-terminal tail and their roles in ATP binding. Acta Crystallogr D Biol Crystallogr. 2010 May;66(Pt 5):577-83. Epub 2010 Apr 21. PMID:20445233 doi:10.1107/S0907444910005639

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3a8x"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of PKCiota kinase domain==
-<StructureSection load='3a8x' size='340' side='right' caption='[[3a8x]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='3a8x' size='340' side='right'caption='[[3a8x]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3a8x]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3A8X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3A8X FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3a8x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3A8X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3A8X FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3a8w|3a8w]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3a8w|3a8w]]</div></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_kinase_C Protein kinase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.13 2.7.11.13] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Protein_kinase_C Protein kinase C], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.13 2.7.11.13] </span></td></tr>
-<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=3a8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3a8x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3a8x RCSB], [http://www.ebi.ac.uk/pdbsum/3a8x PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3a8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3a8x OCA], [https://pdbe.org/3a8x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3a8x RCSB], [https://www.ebi.ac.uk/pdbsum/3a8x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3a8x ProSAT]</span></td></tr>
 </table>
+== Function ==
+[[https://www.uniprot.org/uniprot/KPCI_HUMAN KPCI_HUMAN]] Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis.<ref>PMID:8226978</ref> <ref>PMID:9346882</ref> <ref>PMID:10467349</ref> <ref>PMID:10356400</ref> <ref>PMID:10906326</ref> <ref>PMID:11042363</ref> <ref>PMID:11724794</ref> <ref>PMID:12871960</ref> <ref>PMID:14684752</ref> <ref>PMID:15994303</ref> <ref>PMID:18270268</ref> <ref>PMID:19327373</ref> <ref>PMID:21419810</ref> <ref>PMID:21189248</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a8/3a8x_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a8/3a8x_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3a8x ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 27: / Line 30: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3a8x" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Protein kinase C 3D structures|Protein kinase C 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Protein kinase C]]
-[[Category: Kamata, K.]]
+[[Category: Kamata, K]]
-[[Category: Takimura, T.]]
+[[Category: Takimura, T]]
 [[Category: Protein kinase c iota]]
 [[Category: Transferase]]

3a8x

From Proteopedia

Current revision

Crystal Structure of PKCiota kinase domain

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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