2vx3: Difference between revisions

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-{{Seed}}
-[[Image:2vx3.png|left|200px]]
-<!--
+==Crystal structure of the human dual specificity tyrosine- phosphorylation-regulated kinase 1A==
-The line below this paragraph, containing "STRUCTURE_2vx3", creates the "Structure Box" on the page.
+<StructureSection load='2vx3' size='340' side='right'caption='[[2vx3]], [[Resolution|resolution]] 2.40&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'>[[2vx3]] is a 4 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=2VX3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VX3 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]] 2.4&#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=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-{{STRUCTURE_2vx3|  PDB=2vx3  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vx3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vx3 OCA], [https://pdbe.org/2vx3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vx3 RCSB], [https://www.ebi.ac.uk/pdbsum/2vx3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vx3 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/vx/2vx3_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=2vx3 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.
-===CRYSTAL STRUCTURE OF THE HUMAN DUAL SPECIFICITY TYROSINE-PHOSPHORYLATION-REGULATED KINASE 1A===
+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>
-VX3 is a 4 chains structure of sequences 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=2VX3 OCA].
+<div class="pdbe-citations 2vx3" 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: Arrowsmith CH]]
-[[Category: Burgess-Brown, N.]]
+[[Category: Bountra C]]
-[[Category: Delft, F Von.]]
+[[Category: Burgess-Brown N]]
-[[Category: Edwards, A.]]
+[[Category: Edwards A]]
-[[Category: Fedorov, O.]]
+[[Category: Federov O]]
-[[Category: Filippakopoulos, P.]]
+[[Category: Filippakopoulos P]]
-[[Category: King, O.]]
+[[Category: King O]]
-[[Category: Knapp, S.]]
+[[Category: Knapp S]]
-[[Category: Philips, C.]]
+[[Category: Philips C]]
-[[Category: Pike, A C.W.]]
+[[Category: Pike ACW]]
-[[Category: Roos, A K.]]
+[[Category: Roos AK]]
-[[Category: Soundararajan, M.]]
+[[Category: Soundararajan M]]
-[[Category: Wikstrom, M.]]
+[[Category: Wikstrom M]]
-[[Category: Alternative splicing]]
+[[Category: Von Delft F]]
-[[Category: Atp-binding]]
-[[Category: Casp8]]
-[[Category: Dyrk1a]]
-[[Category: Hp86]]
-[[Category: Kinase]]
-[[Category: Minibrain homolog]]
-[[Category: Mnb]]
-[[Category: Mnbh]]
-[[Category: Nucleotide-binding]]
-[[Category: Nucleus]]
-[[Category: Phosphoprotein]]
-[[Category: Polymorphism]]
-[[Category: Serine/threonine-protein kinase]]
-[[Category: Transferase]]
-[[Category: Tyrosine-protein kinase]]
-[[Category: Yak1-related kinase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 07:13:11 2009''