2wo6: Difference between revisions

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-[[Image:2wo6.png|left|200px]]
-{{STRUCTURE_2wo6|  PDB=2wo6  |  SCENE=  }}
+==Human Dual-Specificity Tyrosine-Phosphorylation-Regulated Kinase 1A in complex with a consensus substrate peptide==
+<StructureSection load='2wo6' size='340' side='right'caption='[[2wo6]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2wo6]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WO6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WO6 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=D15:N-(5-{[(2S)-4-AMINO-2-(3-CHLOROPHENYL)BUTANOYL]AMINO}-1H-INDAZOL-3-YL)BENZAMIDE'>D15</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></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=2wo6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wo6 OCA], [https://pdbe.org/2wo6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wo6 RCSB], [https://www.ebi.ac.uk/pdbsum/2wo6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wo6 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/DYR1A_HUMAN DYR1A_HUMAN] Defects in DYRK1A are the cause of mental retardation autosomal dominant type 7 (MRD7) [MIM:[https://omim.org/entry/614104 614104]. A disease characterized by primary microcephaly, severe mental retardation without speech, anxious autistic behavior, and dysmorphic features, including bitemporal narrowing, deep-set eyes, large simple ears, and a pointed nasal tip. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period.<ref>PMID:21294719</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/DYR1A_HUMAN DYR1A_HUMAN] May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Phosphorylates serine, threonine and tyrosine residues in its sequence and in exogenous substrates.<ref>PMID:8769099</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/wo/2wo6_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2wo6 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinases (DYRKs) play key roles in brain development, regulation of splicing, and apoptosis, and are potential drug targets for neurodegenerative diseases and cancer. We present crystal structures of one representative member of each DYRK subfamily: DYRK1A with an ATP-mimetic inhibitor and consensus peptide, and DYRK2 including NAPA and DH (DYRK homology) box regions. The current activation model suggests that DYRKs are Ser/Thr kinases that only autophosphorylate the second tyrosine of the activation loop YxY motif during protein translation. The structures explain the roles of this tyrosine and of the DH box in DYRK activation and provide a structural model for DYRK substrate recognition. Phosphorylation of a library of naturally occurring peptides identified substrate motifs that lack proline in the P+1 position, suggesting that DYRK1A is not a strictly proline-directed kinase. Our data also show that DYRK1A wild-type and Y321F mutant retain tyrosine autophosphorylation activity.
-===HUMAN DUAL-SPECIFICITY TYROSINE-PHOSPHORYLATION-REGULATED KINASE 1A IN COMPLEX WITH A CONSENSUS SUBSTRATE PEPTIDE===
+Structures of Down Syndrome Kinases, DYRKs, Reveal Mechanisms of Kinase Activation and Substrate Recognition.,Soundararajan M, Roos AK, Savitsky P, Filippakopoulos P, Kettenbach AN, Olsen JV, Gerber SA, Eswaran J, Knapp S, Elkins JM Structure. 2013 Jun 4;21(6):986-96. doi: 10.1016/j.str.2013.03.012. Epub 2013 May, 9. PMID:23665168<ref>PMID:23665168</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-==About this Structure==
+</div>
-[[2wo6]] is a 3 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=2WO6 OCA].
+<div class="pdbe-citations 2wo6" style="background-color:#fffaf0;"></div>
-[[Category: Dual-specificity kinase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Arrowsmith, C H.]]
+[[Category: Large Structures]]
-[[Category: Bountra, C.]]
+[[Category: Synthetic construct]]
-[[Category: Burgess-Brown, N.]]
+[[Category: Arrowsmith CH]]
-[[Category: Delft, F Von.]]
+[[Category: Bountra C]]
-[[Category: Edwards, A.]]
+[[Category: Burgess-Brown N]]
-[[Category: Elkins, J M.]]
+[[Category: Edwards A]]
-[[Category: Eswaran, J.]]
+[[Category: Elkins JM]]
-[[Category: Fedorov, O.]]
+[[Category: Eswaran J]]
-[[Category: Knapp, S.]]
+[[Category: Fedorov O]]
-[[Category: Muniz, J R.C.]]
+[[Category: Knapp S]]
-[[Category: Phillips, C.]]
+[[Category: Muniz JRC]]
-[[Category: Pike, A C.W.]]
+[[Category: Phillips C]]
-[[Category: Roos, A K.]]
+[[Category: Pike ACW]]
-[[Category: Soundararajan, M.]]
+[[Category: Roos AK]]
-[[Category: Ugochukwu, E.]]
+[[Category: Soundararajan M]]
-[[Category: Wikstrom, M.]]
+[[Category: Ugochukwu E]]
-[[Category: Dyrk1]]
+[[Category: Wikstrom M]]
-[[Category: Dyrk1a]]
+[[Category: Von Delft F]]
-[[Category: Kinase]]
-[[Category: Nucleotide-binding]]
-[[Category: Nucleus]]
-[[Category: Phosphoprotein]]
-[[Category: Serine/threonine-protein atp-binding]]
-[[Category: Transferase]]
-[[Category: Transferase peptide complex]]
-[[Category: Transferase-peptide complex]]
-[[Category: Tyrosine-protein kinase]]