title: A structurally driven analysis of thiol reactivity in mammalian albumins.
abstract: Understanding the structural basis of protein redox activity is still an open question. Hence, by using a structural genomics approach, different albumins have been chosen to correlate protein structural features with the corresponding reaction rates of thiol exchange between albumin and disulfide DTNB. Predicted structures of rat, porcine, and bovine albumins have been compared with the experimentally derived human albumin. High structural similarity among these four albumins can be observed, in spite of their markedly different reactivity with DTNB. Sequence alignments offered preliminary hints on the contributions of sequence-specific local environments modulating albumin reactivity. Molecular dynamics simulations performed on experimental and predicted albumin structures reveal that thiolation rates are influenced by hydrogen bonding pattern and stability of the acceptor C34 sulphur atom with donor groups of nearby residues. Atom depth evolution of albumin C34 thiol groups has been monitored during Molecular Dynamic trajectories. The most reactive albumins appeared also the ones presenting the C34 sulphur atom on the protein surface with the highest accessibility. High C34 sulphur atom reactivity in rat and porcine albumins seems to be determined by the presence of additional positively charged amino acid residues favoring both the C34 S⁻ form and the approach of DTNB.
authors.affiliation: Department of Molecular Biology, University of Siena and SienaBiografix Srl, Siena 53100, Italy.
authors.forename: Ottavia
authors.initials: O
authors.lastname: Spiga
authors.forename: Domenico
authors.initials: D
authors.lastname: Summa
authors.forename: Simone
authors.initials: S
authors.lastname: Cirri
authors.forename: Andrea
authors.initials: A
authors.lastname: Bernini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Venditti
authors.forename: Matteo
authors.initials: M
authors.lastname: De Chiara
authors.forename: Raffaella
authors.initials: R
authors.lastname: Priora
authors.forename: Simona
authors.initials: S
authors.lastname: Frosali
authors.forename: Antonios
authors.initials: A
authors.lastname: Margaritis
authors.forename: Danila
authors.initials: D
authors.lastname: Di Giuseppe
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Simplicio
authors.forename: Neri
authors.initials: N
authors.lastname: Niccolai
mesh_terms: D000418:Albumins / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D004220:Disulfides / Q000737:chemistry*; D004228:Dithionitrobenzoic Acid / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats; D016415:Sequence Alignment / Q000379:methods*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D000418:Albumins; D004220:Disulfides; D013438:Sulfhydryl Compounds; D004228:Dithionitrobenzoic Acid