A structurally driven analysis of thiol reactivity in mammalian albumins
| Autor: | Simone Cirri, Simona Frosali, Andrea Bernini, Domenico Summa, Neri Niccolai, Danila Di Giuseppe, Paolo Di Simplicio, Matteo De Chiara, Antonios Margaritis, Raffaella Priora, Ottavia Spiga, Vincenzo Venditti |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Stereochemistry DTNB Protein Conformation Molecular Sequence Data Biophysics Dithionitrobenzoic Acid Biochemistry Structural genomics Biomaterials Molecular dynamics Albumins Organic chemistry Animals Humans Reactivity (chemistry) Homology modeling Amino Acid Sequence Disulfides Sulfhydryl Compounds chemistry.chemical_classification Hydrogen bond Organic Chemistry Albumin Hydrogen Bonding General Medicine Hydrogen-Ion Concentration Protein Structure Tertiary Rats chemistry Thiol Cattle Sequence Alignment |
| Popis: | 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. © 2010 Wiley Periodicals, Inc. Biopolymers 95:278–285, 2011. |
| Databáze: | OpenAIRE |
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