title: Can enzymatic activity, or otherwise, be inferred from structural studies of annexin III?
abstract: Annexin III, a putative inositol (1,2)-phosphohydrolase, was co-crystallized with inositol 2-phosphate, the inhibitor of the reaction, and its structure was solved to 1.95 A resolution. No enzyme active site was observed in the structure. Assays for enzymatic activity were also negative. Search for annexin III-inositol phosphate interactions using the BIAcoreTM system revealed an affinity for inositol cyclic (1,2)-phosphate, suggesting annexin III may sequester the molecule in the cell. The BIAcoreTM system used with different phospholipids showed that annexin III displays specificity for phosphatidylethanolamine, but not for phosphatidylinositols. Interestingly, a molecule of ethanolamine was found bound to the protein in the crystal structure. Coupled with the fact that this is a particularly abundant phospholipid in granules specific to neutrophils, cells where annexin III is highly expressed, our finding could be pointing to a physiological role of annexin III.
authors.affiliation: Institut Cochin de Génétique Moléculaire, U332 INSERM, 22 rue Méchain, 75014 Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Perron
authors.forename: A
authors.initials: A
authors.lastname: Lewit-Bentley
authors.forename: B
authors.initials: B
authors.lastname: Geny
authors.forename: F
authors.initials: F
authors.lastname: Russo-Marie
mesh_terms: D017318:Annexin A3 / Q000737:chemistry* / Q000378:metabolism; D015374:Biosensing Techniques; D002384:Catalysis; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry*; D007295:Inositol Phosphates / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors*; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; D010714:Phosphatidylethanolamines; D010743:Phospholipids; C010199:inositol cyclic phosphate; C047872:inositol 2-monophosphate; D010744:Phosphoric Monoester Hydrolases; D017318:Annexin A3