1p4f: Difference between revisions

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-{{Seed}}
-[[Image:1p4f.png|left|200px]]
-<!--
+==DEATH ASSOCIATED PROTEIN KINASE CATALYTIC DOMAIN WITH BOUND INHIBITOR FRAGMENT==
-The line below this paragraph, containing "STRUCTURE_1p4f", creates the "Structure Box" on the page.
+<StructureSection load='1p4f' size='340' side='right'caption='[[1p4f]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1p4f]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P4F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P4F FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=86Q:5,6-Dihydro-benzo[H]cinnolin-3-ylamine'>86Q</scene></td></tr>
-{{STRUCTURE_1p4f|  PDB=1p4f  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1p4f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p4f OCA], [https://pdbe.org/1p4f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p4f RCSB], [https://www.ebi.ac.uk/pdbsum/1p4f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p4f ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/DAPK1_HUMAN DAPK1_HUMAN] Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition.<ref>PMID:7828849</ref> <ref>PMID:10629061</ref> <ref>PMID:11579085</ref> <ref>PMID:11980920</ref> <ref>PMID:12730201</ref> <ref>PMID:15367680</ref> <ref>PMID:17703233</ref> <ref>PMID:17895359</ref> <ref>PMID:18422656</ref> <ref>PMID:18195017</ref> <ref>PMID:18995835</ref> <ref>PMID:19180116</ref> <ref>PMID:18974095</ref> <ref>PMID:21497122</ref> <ref>PMID:21408167</ref>   Isoform 2 cannot induce apoptosis but can induce membrane blebbing.<ref>PMID:7828849</ref> <ref>PMID:10629061</ref> <ref>PMID:11579085</ref> <ref>PMID:11980920</ref> <ref>PMID:12730201</ref> <ref>PMID:15367680</ref> <ref>PMID:17703233</ref> <ref>PMID:17895359</ref> <ref>PMID:18422656</ref> <ref>PMID:18195017</ref> <ref>PMID:18995835</ref> <ref>PMID:19180116</ref> <ref>PMID:18974095</ref> <ref>PMID:21497122</ref> <ref>PMID:21408167</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/p4/1p4f_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/main_output.php?pdb_ID=1p4f ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Death associated protein kinase (DAPK) is a calcium and calmodulin regulated enzyme that functions early in eukaryotic programmed cell death, or apoptosis. To validate DAPK as a potential drug discovery target for acute brain injury, the first small molecule DAPK inhibitor was synthesized and tested in vivo. A single injection of the aminopyridazine-based inhibitor administered 6 h after injury attenuated brain tissue or neuronal biomarker loss measured, respectively, 1 week and 3 days later. Because aminopyridazine is a privileged structure in neuropharmacology, we determined the high-resolution crystal structure of a binary complex between the kinase domain and a molecular fragment of the DAPK inhibitor. The co-crystal structure describes a structural basis for interaction and provides a firm foundation for structure-assisted design of lead compounds with appropriate molecular properties for future drug development.
-===DEATH ASSOCIATED PROTEIN KINASE CATALYTIC DOMAIN WITH BOUND INHIBITOR FRAGMENT===
+An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury.,Velentza AV, Wainwright MS, Zasadzki M, Mirzoeva S, Schumacher AM, Haiech J, Focia PJ, Egli M, Watterson DM Bioorg Med Chem Lett. 2003 Oct 20;13(20):3465-70. PMID:14505650<ref>PMID:14505650</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1p4f" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_14505650}}, adds the Publication Abstract to the page
+*[[Death-associated protein kinase 3D structures|Death-associated protein kinase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 14505650 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_14505650}}
+__TOC__
+</StructureSection>
-==About this Structure==
-P4F is a 1 chain structure of 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=1P4F OCA].
-==Reference==
-<ref group="xtra">PMID:14505650</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Egli, M.]]
+[[Category: Large Structures]]
-[[Category: Focia, P J.]]
+[[Category: Egli M]]
-[[Category: Haiech, J.]]
+[[Category: Focia PJ]]
-[[Category: Mirzoeva, S.]]
+[[Category: Haiech J]]
-[[Category: Velentza, A V.]]
+[[Category: Mirzoeva S]]
-[[Category: Wainwright, M S.]]
+[[Category: Velentza AV]]
-[[Category: Watterson, D M.]]
+[[Category: Wainwright MS]]
-[[Category: Zasadzki, M.]]
+[[Category: Watterson DM]]
-[[Category: Kinase]]
+[[Category: Zasadzki M]]
-[[Category: Transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 20:09:23 2009''