2wei: Difference between revisions

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-[[Image:2wei.png|left|200px]]
-{{STRUCTURE_2wei|  PDB=2wei  |  SCENE=  }}
+==Crystal structure of the kinase domain of Cryptosporidium parvum calcium dependent protein kinase in complex with 3-MB-PP1==
+<StructureSection load='2wei' size='340' side='right'caption='[[2wei]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2wei]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptosporidium_parvum_Iowa_II Cryptosporidium parvum Iowa II]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WEI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WEI 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]] 1.65&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VGG:1-TERT-BUTYL-3-(3-METHYLBENZYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE'>VGG</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=2wei FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wei OCA], [https://pdbe.org/2wei PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wei RCSB], [https://www.ebi.ac.uk/pdbsum/2wei PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wei ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/A3FQ16_CRYPI A3FQ16_CRYPI]
+== 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/we/2wei_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=2wei ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+ABSTRACT: BACKGROUND: Hundreds of millions of people are infected with cryptosporidiosis annually, with immunocompromised individuals suffering debilitating symptoms and children in socioeconomically challenged regions at risk of repeated infections. There is currently no effective drug available. In order to facilitate the pursuit of anti-cryptosporidiosis targets and compounds, our study spans the classification of the Cryptosporidium parvum kinome and the structural and biochemical characterization of representatives from the CDPK family and a MAP kinase. RESULTS: The C. parvum kinome comprises over 70 members, some of which may be promising drug targets. These C. parvum protein kinases include members in the AGC, Atypical, CaMK, CK1, CMGC, and TKL groups; however, almost 35 % could only be classified as OPK (other protein kinases). In addition, about 25 % of the kinases identified did not have any known orthologues outside of Cryptosporidium spp. Comparison of specific kinases with their Plasmodium falciparum and Toxoplasma gondii orthologues revealed some distinct characteristics within the C. parvum kinome, including potential targets and opportunities for drug design. Structural and biochemical analysis of 4 representatives of the CaMK group and a MAP kinase confirms features that may be exploited in inhibitor design. Indeed, screening CpCDPK1 against a library of kinase inhibitors yielded a set of the pyrazolopyrimidine derivatives (PP1-derivatives) with IC50 values of &lt;10 nM. The binding of a PP1-derivative is further described by an inhibitor-bound crystal structure of CpCDPK1. In addition, structural analysis of CpCDPK4 identified an unprecedented Zn-finger within the CDPK kinase domain that may have implications for its regulation. CONCLUSIONS: Identification and comparison of the C. parvum protein kinases against other parasitic kinases shows how orthologue- and family-based research can be used to facilitate characterization of promising drug targets and the search for new drugs.
-===Crystal structure of the kinase domain of Cryptosporidium parvum calcium dependent protein kinase in complex with 3-MB-PP1===
+The Cryptosporidium parvum Kinome.,Artz JD, Wernimont AK, Allali-Hassani A, Zhao Y, Amani M, Lin YH, Senisterra G, Wasney GA, Fedorov O, King O, Roos A, Lunin VV, Qiu W, Finerty P Jr, Hutchinson A, Chau I, von Delft F, Mackenzie F, Lew J, Kozieradzki I, Vedadi M, Schapira M, Zhang C, Shokat K, Heightman T, Hui R BMC Genomics. 2011 Sep 30;12(1):478. PMID:21962082<ref>PMID:21962082</ref>
-{{ABSTRACT_PUBMED_21962082}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 2wei" style="background-color:#fffaf0;"></div>
-[[2wei]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryptosporidium_parvum_iowa_ii Cryptosporidium parvum iowa ii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WEI OCA].
+== References ==
+<references/>
-==Reference==
+__TOC__
-<ref group="xtra">PMID:021962082</ref><references group="xtra"/>
+</StructureSection>
-[[Category: Cryptosporidium parvum iowa ii]]
+[[Category: Cryptosporidium parvum Iowa II]]
-[[Category: Xylulokinase]]
+[[Category: Large Structures]]
-[[Category: Arrowsmith, C H.]]
+[[Category: Arrowsmith CH]]
-[[Category: Artz, J D.]]
+[[Category: Artz JD]]
-[[Category: Bountra, C.]]
+[[Category: Bountra C]]
-[[Category: Chaikuad, A.]]
+[[Category: Chaikuad A]]
-[[Category: Delft, F Von.]]
+[[Category: Doyle D]]
-[[Category: Doyle, D.]]
+[[Category: Edwards A]]
-[[Category: Edwards, A.]]
+[[Category: Fedorov O]]
-[[Category: Fedorov, O.]]
+[[Category: Finerty PJ]]
-[[Category: Finerty, P J.]]
+[[Category: Heightman T]]
-[[Category: Heightman, T.]]
+[[Category: Hui R]]
-[[Category: Hui, R.]]
+[[Category: Indarte M]]
-[[Category: Indarte, M.]]
+[[Category: King O]]
-[[Category: King, O.]]
+[[Category: Kozieradzki I]]
-[[Category: Kozieradzki, I.]]
+[[Category: Lin L]]
-[[Category: Lin, L.]]
+[[Category: MacKenzie FI]]
-[[Category: Mackenzie, F I.]]
+[[Category: Muniz J]]
-[[Category: Muniz, J.]]
+[[Category: Pike ACW]]
-[[Category: Pike, A C.W.]]
+[[Category: Roos AK]]
-[[Category: Roos, A K.]]
+[[Category: Schapira M]]
-[[Category: Schapira, M.]]
+[[Category: Shokat KM]]
-[[Category: Shokat, K M.]]
+[[Category: Vedadi M]]
-[[Category: Vedadi, M.]]
+[[Category: Weigelt J]]
-[[Category: Weigelt, J.]]
+[[Category: Wernimont AK]]
-[[Category: Wernimont, A K.]]
+[[Category: Zhang C]]
-[[Category: Zhang, C.]]
+[[Category: Von Delft F]]
-[[Category: Atp-binding]]
-[[Category: Kinase]]
-[[Category: Nucleotide-binding]]
-[[Category: Serine/threonine-protein kinase]]
-[[Category: Transferase]]