title: All-trans-retinoic acid and retinol binding to the FA1 site of human serum albumin competitively inhibits heme-Fe(III) association.
abstract: Retinoids are a class of chemicals derived from vitamin A metabolism, playing important and diverse functions. Vitamin A, also named all-trans-retinol (all-trans-ROL), is coverted into two classes of biologically active retinoids, i.e. 11-cis-retinoids and acidic retinoids. Among acidic retinoids, all-trans-retinoic acid (all-trans-RA) and 9-cis-retinoic acid (9-cis-RA) represent the main metabolic products. Specific and aspecific proteins solubilize, protect, and detoxify retinoids in the extracellular environment. The retinoid binding protein 4 (RBP4), the epididymal retinoid-binding protein (ERBP), and the interphotoreceptor matrix retinoid-binding protein (IRBP) play a central role in ROL transport, whereas lipocalin-type prostaglandin D synthase (also named β-trace) and human serum albumin (HSA) transport preferentially all-trans-RA. Here, the modulatory effect of all-trans-RA and all-trans-ROL on ferric heme (heme-Fe(III)) binding to HSA is reported. All-trans-RA and all-trans-ROL binding to the FA1 site of HSA competitively inhibit heme-Fe(III) association. Docking simulations and local structural comparison of HSA with all-trans-RA- and all-trans-ROL-binding proteins support functional data indicating the preferential binding of all-trans-RA and all-trans-ROL to the FA1 site of HSA. Present results may be relevant in vivo, in fact HSA could act as a secondary carrier of retinoids in human diseases associated with reduced levels of RBP4 and IRBP.
authors.affiliation: Department of Sciences, Roma Tre University, I-00146 Roma, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Di Muzio
authors.affiliation: Department of Sciences, Roma Tre University, I-00146 Roma, Italy; National Institute of Nuclear Physics, Roma Tre Section, I-00146 Roma, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Polticelli
authors.affiliation: Department of Sciences, Roma Tre University, I-00146 Roma, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: di Masi
authors.affiliation: Division of Biomedical Sciences, Department of Theoretical and Applied Sciences, University of Insubria, I-21052 Busto Arsizio (VA), Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fanali
authors.affiliation: Division of Biomedical Sciences, Department of Theoretical and Applied Sciences, University of Insubria, I-21052 Busto Arsizio (VA), Italy; Center of Neuroscience, University of Insubria, I-21052 Busto Arsizio (VA), Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Fasano
authors.affiliation: Interdepartmental Laboratory for Electron Microscopy, Roma Tre University, I-00146 Roma, Italy. Electronic address: ascenzi@uniroma3.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
mesh_terms: D001665:Binding Sites; D006418:Heme / Q000737:chemistry*; D006801:Humans; D007501:Iron / Q000737:chemistry; D008956:Models, Chemical; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011487:Protein Conformation; D012709:Serum Albumin / Q000737:chemistry* / Q000648:ultrastructure*; D014212:Tretinoin / Q000737:chemistry*; D014801:Vitamin A / Q000737:chemistry*
chemical_list: D012709:Serum Albumin; D014801:Vitamin A; D006418:Heme; D014212:Tretinoin; D007501:Iron
keywords: All-trans-retinoic acid; Competitive inhibition; Heme binding; Human serum albumin; Molecular docking; Retinol