4otd: Difference between revisions
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<StructureSection load='4otd' size='340' side='right' caption='[[4otd]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='4otd' size='340' side='right' caption='[[4otd]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4otd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OTD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OTD FirstGlance]. <br> | <table><tr><td colspan='2'>[[4otd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OTD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OTD FirstGlance]. <br> | ||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4otg|4otg]], [[4oth|4oth]], [[4oti|4oti]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4otg|4otg]], [[4oth|4oth]], [[4oti|4oti]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PKN1, PAK1, PKN, PRK1, PRKCL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[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='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=4otd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4otd OCA], [http://pdbe.org/4otd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4otd RCSB], [http://www.ebi.ac.uk/pdbsum/4otd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4otd ProSAT]</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=4otd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4otd OCA], [http://pdbe.org/4otd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4otd RCSB], [http://www.ebi.ac.uk/pdbsum/4otd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4otd ProSAT]</span></td></tr> | ||
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==See Also== | ==See Also== | ||
*[[Student Project 1 for UMass Chemistry 423 Spring 2015|Student Project 1 for UMass Chemistry 423 Spring 2015]] | *[[Student Project 1 for UMass Chemistry 423 Spring 2015|Student Project 1 for UMass Chemistry 423 Spring 2015]] | ||
== References == | == References == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Protein kinase C]] | [[Category: Protein kinase C]] | ||
[[Category: Abbassian, M]] | [[Category: Abbassian, M]] | ||
[[Category: Cathers, B]] | [[Category: Cathers, B]] | ||
[[Category: Chamberlain, P P]] | [[Category: Chamberlain, P P]] | ||
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[[Category: Mahmoudi, A]] | [[Category: Mahmoudi, A]] | ||
[[Category: Muir, J]] | [[Category: Muir, J]] | ||
[[Category: Pagarigan, B]] | |||
[[Category: Raheja, N]] | [[Category: Raheja, N]] | ||
[[Category: Atp binding]] | [[Category: Atp binding]] | ||
Revision as of 23:15, 24 January 2018
Crystal Structure of PRK1 Catalytic DomainCrystal Structure of PRK1 Catalytic Domain
Structural highlights
Function[PKN1_HUMAN] PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro.[1] [2] [3] [4] [5] [6] [7] [8] [9] Publication Abstract from PubMedProtein kinase C related kinase 1 (PRK1) is a component of Rho-GTPase, androgen receptor, histone demethylase and histone deacetylase signaling pathways implicated in prostate and ovarian cancer. Herein we describe the crystal structure of PRK1 in apo form, and also in complex with a panel of literature inhibitors including the clinical candidates lestaurtinib and tofacitinib, as well as the staurosporine analog Ro-31-8220. PRK1 is a member of the AGC-kinase class, and as such exhibits the characteristic regulatory sequence at the C-terminus of the catalytic domain - the 'C-tail'. The C-tail fully encircles the catalytic domain placing a phenylalanine in the ATP-binding site. Our inhibitor structures include examples of molecules which both interact with, and displace the C-tail from the active site. This information may assist in the design of inhibitors targeting both PRK and other members of the AGC kinase family. Crystal Structures of PRK1 in Complex with the Clinical Compounds Lestaurtinib and Tofacitinib Reveal Ligand Induced Conformational Changes.,Chamberlain P, Delker S, Pagarigan B, Mahmoudi A, Jackson P, Abbasian M, Muir J, Raheja N, Cathers B PLoS One. 2014 Aug 11;9(8):e103638. doi: 10.1371/journal.pone.0103638., eCollection 2014. PMID:25111382[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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