4bgq: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-{{STRUCTURE_4bgq|  PDB=4bgq  |  SCENE=  }}
-===Crystal structure of the human CDKL5 kinase domain===
-==Disease==
+==Crystal structure of the human CDKL5 kinase domain==
-[[http://www.uniprot.org/uniprot/CDKL5_HUMAN CDKL5_HUMAN]] Note=Chromosomal aberrations involving CDKL5 are found in patients manifesting early-onset seizures and spams and psychomotor impairment. Translocation t(X;6)(p22.3;q14); translocation t(X;7)(p22.3;p15).  Epileptic encephalopathy, early infantile, 2 (EIEE2) [MIM:[http://omim.org/entry/300672 300672]]: A severe form of epilepsy characterized by seizures or spasms beginning in infancy. Patients with epileptic encephalopathy early infantile type 2 manifest features resembling Rett syndrome such as microcephaly, lack of speech development, stereotypic hand movements. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:15917271</ref> <ref>PMID:16935860</ref> <ref>PMID:12736870</ref> <ref>PMID:15492925</ref> <ref>PMID:15499549</ref> <ref>PMID:15689447</ref> <ref>PMID:16015284</ref> <ref>PMID:16611748</ref> <ref>PMID:18790821</ref> <ref>PMID:17993579</ref> <ref>PMID:18809835</ref> <ref>PMID:19253388</ref> <ref>PMID:19241098</ref>
+<StructureSection load='4bgq' size='340' side='right'caption='[[4bgq]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4bgq]] 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=4BGQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BGQ 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&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=38R:[4-({4-[(3-CYCLOPENTYL-1H-PYRAZOL-5-YL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETONITRILE'>38R</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=4bgq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bgq OCA], [https://pdbe.org/4bgq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bgq RCSB], [https://www.ebi.ac.uk/pdbsum/4bgq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bgq ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/CDKL5_HUMAN CDKL5_HUMAN] Note=Chromosomal aberrations involving CDKL5 are found in patients manifesting early-onset seizures and spams and psychomotor impairment. Translocation t(X;6)(p22.3;q14); translocation t(X;7)(p22.3;p15).  Epileptic encephalopathy, early infantile, 2 (EIEE2) [MIM:[https://omim.org/entry/300672 300672]: A severe form of epilepsy characterized by seizures or spasms beginning in infancy. Patients with epileptic encephalopathy early infantile type 2 manifest features resembling Rett syndrome such as microcephaly, lack of speech development, stereotypic hand movements. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:15917271</ref> <ref>PMID:16935860</ref> <ref>PMID:12736870</ref> <ref>PMID:15492925</ref> <ref>PMID:15499549</ref> <ref>PMID:15689447</ref> <ref>PMID:16015284</ref> <ref>PMID:16611748</ref> <ref>PMID:18790821</ref> <ref>PMID:17993579</ref> <ref>PMID:18809835</ref> <ref>PMID:19253388</ref> <ref>PMID:19241098</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/CDKL5_HUMAN CDKL5_HUMAN] Mediates phosphorylation of MECP2.<ref>PMID:15917271</ref> <ref>PMID:16935860</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Various kinases, including a cyclin-dependent kinase (CDK) family member, regulate the growth and functions of primary cilia, which perform essential roles in signaling and development. Neurological disorders linked to CDK-Like (CDKL) proteins suggest that these underexplored kinases may have similar functions. Here, we present the crystal structures of human CDKL1, CDKL2, CDKL3, and CDKL5, revealing their evolutionary divergence from CDK and mitogen-activated protein kinases (MAPKs), including an unusual ?J helix important for CDKL2 and CDKL3 activity. C. elegans CDKL-1, most closely related to CDKL1-4 and localized to neuronal cilia transition zones, modulates cilium length; this depends on its kinase activity and ?J helix-containing C terminus. Human CDKL5, linked to Rett syndrome, also localizes to cilia, and it impairs ciliogenesis when overexpressed. CDKL5 patient mutations modeled in CDKL-1 cause localization and/or cilium length defects. Together, our studies establish a disease model system suggesting cilium length defects as a pathomechanism for neurological disorders, including epilepsy.
-==Function==
+CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function.,Canning P, Park K, Goncalves J, Li C, Howard CJ, Sharpe TD, Holt LJ, Pelletier L, Bullock AN, Leroux MR Cell Rep. 2018 Jan 23;22(4):885-894. doi: 10.1016/j.celrep.2017.12.083. Epub 2018, Jan 28. PMID:29420175<ref>PMID:29420175</ref>
-[[http://www.uniprot.org/uniprot/CDKL5_HUMAN CDKL5_HUMAN]] Mediates phosphorylation of MECP2.<ref>PMID:15917271</ref> <ref>PMID:16935860</ref>
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[4bgq]] is a 1 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=4BGQ OCA].
+</div>
+<div class="pdbe-citations 4bgq" style="background-color:#fffaf0;"></div>
-==Reference==
+== References ==
-<references group="xtra"/><references/>
+<references/>
-[[Category: Cyclin-dependent kinase]]
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Arrowsmith, C H.]]
+[[Category: Large Structures]]
-[[Category: Bountra, C.]]
+[[Category: Arrowsmith CH]]
-[[Category: Bullock, A.]]
+[[Category: Bountra C]]
-[[Category: Canning, P.]]
+[[Category: Bullock A]]
-[[Category: Delft, F von.]]
+[[Category: Canning P]]
-[[Category: Edwards, A M.]]
+[[Category: Edwards AM]]
-[[Category: Goubin, S.]]
+[[Category: Goubin S]]
-[[Category: Krojer, T.]]
+[[Category: Krojer T]]
-[[Category: Mahajan, P.]]
+[[Category: Mahajan P]]
-[[Category: Pike, A C.W.]]
+[[Category: Pike ACW]]
-[[Category: Vollmar, M.]]
+[[Category: Vollmar M]]
-[[Category: Kinase]]
+[[Category: Von Delft F]]
-[[Category: Phospho-mimetic]]
-[[Category: Transferase]]