1o7k
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1o7k |SIZE=350|CAPTION= <scene name='initialview01'>1o7k</scene>, resolution 2.0Å | |PDB= 1o7k |SIZE=350|CAPTION= <scene name='initialview01'>1o7k</scene>, resolution 2.0Å | ||
|SITE= <scene name='pdbsite=API:Second+Anionic+Lipid+Binding+Site.+Chain+C'>API</scene> | |SITE= <scene name='pdbsite=API:Second+Anionic+Lipid+Binding+Site.+Chain+C'>API</scene> | ||
| - | |LIGAND= <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene> | + | |LIGAND= <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1o7k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o7k OCA], [http://www.ebi.ac.uk/pdbsum/1o7k PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1o7k RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Chronic granulomatous disease due to deficiency of NCF-1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608512 608512]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 30: | Line 30: | ||
[[Category: Perisic, O.]] | [[Category: Perisic, O.]] | ||
[[Category: Williams, R L.]] | [[Category: Williams, R L.]] | ||
| - | [[Category: SO4]] | ||
[[Category: nadph oxidase]] | [[Category: nadph oxidase]] | ||
[[Category: p47]] | [[Category: p47]] | ||
| Line 38: | Line 37: | ||
[[Category: sh3 domain]] | [[Category: sh3 domain]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:40:58 2008'' |
Revision as of 19:40, 30 March 2008
| |||||||
| , resolution 2.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN P47 PX DOMAIN COMPLEX WITH SULPHATES
Overview
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.
About this Structure
1O7K is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Sun Mar 30 22:40:58 2008
