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| - | [[Image:2i5c.jpg|left|200px]] | |
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| - | {{Structure
| + | ==Crystal structure of the C-terminal PH domain of pleckstrin in complex with D-myo-Ins(1,2,3,4,5)P5== |
| - | |PDB= 2i5c |SIZE=350|CAPTION= <scene name='initialview01'>2i5c</scene>, resolution 1.75Å
| + | <StructureSection load='2i5c' size='340' side='right'caption='[[2i5c]], [[Resolution|resolution]] 1.75Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=IP5:(1R,2S,3R,4S,5S,6R)-6-HYDROXYCYCLOHEXANE-1,2,3,4,5-PENTAYL PENTAKIS[DIHYDROGEN (PHOSPHATE)]'>IP5</scene> | + | <table><tr><td colspan='2'>[[2i5c]] is a 3 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=2I5C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I5C FirstGlance]. <br> |
| - | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75Å</td></tr> |
| - | |GENE= PLEK, P47 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IP5:(1R,2S,3R,4S,5S,6R)-6-HYDROXYCYCLOHEXANE-1,2,3,4,5-PENTAYL+PENTAKIS[DIHYDROGEN+(PHOSPHATE)]'>IP5</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=2i5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i5c OCA], [https://pdbe.org/2i5c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i5c RCSB], [https://www.ebi.ac.uk/pdbsum/2i5c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i5c ProSAT]</span></td></tr> |
| - | | + | </table> |
| - | '''Crystal structure of the C-terminal PH domain of pleckstrin in complex with D-myo-Ins(1,2,3,4,5)P5'''
| + | == Function == |
| - | | + | [https://www.uniprot.org/uniprot/PLEK_HUMAN PLEK_HUMAN] Major protein kinase C substrate of platelets. |
| - | | + | == Evolutionary Conservation == |
| - | ==Overview==
| + | [[Image:Consurf_key_small.gif|200px|right]] |
| - | BACKGROUND: Pleckstrin homology (PH) domains are one of the most prevalent domains in the human proteome and represent the major phosphoinositide-binding module. These domains are often found in signaling proteins and function predominately by targeting their host proteins to the cell membrane. Inositol phosphates, which are structurally similar to phosphoinositides, are not only known to play a role as signaling molecules but are also capable of being bound by PH domains. RESULTS: In the work presented here it is shown that the addition of commercial myo-inositol hexakisphosphate (IP6) inhibited the binding of the carboxy terminal PH domain of pleckstrin (C-PH) to phosphatidylinositol 3,4-bisphosphate with an IC50 of 7.5 muM. In an attempt to characterize this binding structurally, C-PH was crystallized in the presence of IP6 and the structure was determined to 1.35 A. Examination of the resulting electron density unexpectedly revealed the bound ligand to be D-myo-inositol 1,2,3,5,6-pentakisphosphate. CONCLUSION: The discovery of D-myo-inositol 1,2,3,5,6-pentakisphosphate in the crystal structure suggests that the inhibitory effects observed in the binding studies may be due to this ligand rather than IP6. Analysis of the protein-ligand interaction demonstrated that this myo-inositol pentakisphosphate isomer interacts specifically with protein residues known to be involved in phosphoinositide binding. In addition to this, a structural alignment of other PH domains bound to inositol phosphates containing either four or five phosphate groups revealed that the majority of phosphate groups occupy conserved locations in the binding pockets of PH domains. These findings, taken together with other recently reported studies suggest that myo-inositol pentakisphosphates could act to regulate PH domain-phosphoinositide interactions by directly competing for binding, thus playing an important role as signaling molecules.
| + | Check<jmol> |
| - | | + | <jmolCheckbox> |
| - | ==Disease== | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i5/2i5c_consurf.spt"</scriptWhenChecked> |
| - | Known disease associated with this structure: Age-related maculopathy, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607772 607772]]
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | | + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | ==About this Structure== | + | </jmolCheckbox> |
| - | 2I5C is a [[Single protein]] 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=2I5C OCA].
| + | </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=2i5c ConSurf]. |
| - | | + | <div style="clear:both"></div> |
| - | ==Reference== | + | __TOC__ |
| - | Structural analysis of the carboxy terminal PH domain of pleckstrin bound to D-myo-inositol 1,2,3,5,6-pentakisphosphate., Jackson SG, Zhang Y, Haslam RJ, Junop MS, BMC Struct Biol. 2007 Nov 22;7:80. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18034889 18034889]
| + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Haslam, R J.]] | + | [[Category: Haslam RJ]] |
| - | [[Category: Jackson, S G.]] | + | [[Category: Jackson SG]] |
| - | [[Category: Junop, M S.]] | + | [[Category: Junop MS]] |
| - | [[Category: IP5]]
| + | |
| - | [[Category: lipid binding protein]]
| + | |
| - | [[Category: ph domain]]
| + | |
| - | [[Category: protein-inositol phosphate complex]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:25:39 2008''
| + | |
