1o7k
From Proteopedia
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| - | {{STRUCTURE_1o7k| PDB=1o7k | SCENE= }} | ||
| - | ===HUMAN P47 PX DOMAIN COMPLEX WITH SULPHATES=== | ||
| - | {{ABSTRACT_PUBMED_12356722}} | ||
| - | == | + | ==human p47 PX domain complex with sulphates== |
| - | [[1o7k]] is a 3 chain structure with sequence from [ | + | <StructureSection load='1o7k' size='340' side='right'caption='[[1o7k]], [[Resolution|resolution]] 2.00Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1o7k]] 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=1O7K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1O7K 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]] 2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1o7k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o7k OCA], [https://pdbe.org/1o7k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1o7k RCSB], [https://www.ebi.ac.uk/pdbsum/1o7k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1o7k ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/NCF1_HUMAN NCF1_HUMAN] Defects in NCF1 are the cause of chronic granulomatous disease autosomal recessive cytochrome-b-positive type 1 (CGD1) [MIM:[https://omim.org/entry/233700 233700]. Chronic granulomatous disease is a genetically heterogeneous disorder characterized by the inability of neutrophils and phagocytes to kill microbes that they have ingested. Patients suffer from life-threatening bacterial/fungal infections.<ref>PMID:2011585</ref> <ref>PMID:11133775</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/NCF1_HUMAN NCF1_HUMAN] NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production).<ref>PMID:19801500</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/o7/1o7k_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=1o7k ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | p47(phox) is a key cytosolic subunit required for activation of phagocyte NADPH oxidase. The X-ray structure of the p47(phox) PX domain revealed two distinct basic pockets on the membrane-binding surface, each occupied by a sulfate. These two pockets have different specificities: one preferentially binds phosphatidylinositol 3,4-bisphosphate [PtdIns(3,4)P(2)] and is analogous to the phophatidylinositol 3-phosphate (PtdIns3P)-binding pocket of p40(phox), while the other binds anionic phospholipids such as phosphatidic acid (PtdOH) or phosphatidylserine. The preference of this second site for PtdOH may be related to previously observed activation of NADPH oxidase by PtdOH. Simultaneous occupancy of the two phospholipid-binding pockets radically increases membrane affinity. Strikingly, measurements for full-length p47(phox) show that membrane interaction by the PX domain is masked by an intramolecular association with the C-terminal SH3 domain (C-SH3). Either a site-specific mutation in C-SH3 (W263R) or a mimic of the phosphorylated form of p47(phox) [Ser(303, 304, 328, 359, 370)Glu] cause a transition from a closed to an open conformation that binds membranes with a greater affinity than the isolated PX domain. | ||
| - | + | Binding of the PX domain of p47(phox) to phosphatidylinositol 3,4-bisphosphate and phosphatidic acid is masked by an intramolecular interaction.,Karathanassis D, Stahelin RV, Bravo J, Perisic O, Pacold CM, Cho W, Williams RL EMBO J. 2002 Oct 1;21(19):5057-68. PMID:12356722<ref>PMID:12356722</ref> | |
| - | <ref | + | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 1o7k" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[NADPH oxidase 3D structures|NADPH oxidase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Bravo | + | [[Category: Large Structures]] |
| - | [[Category: Karathanassis | + | [[Category: Bravo J]] |
| - | [[Category: Pacold | + | [[Category: Karathanassis D]] |
| - | [[Category: Perisic | + | [[Category: Pacold CM]] |
| - | [[Category: Williams | + | [[Category: Perisic O]] |
| - | + | [[Category: Williams RL]] | |
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Current revision
human p47 PX domain complex with sulphates
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