title: Limited tendency of alpha-helical residues to form disulfide bridges: a structural explanation.
abstract: Disulfide bridges have an enormous impact on the structure of a large number of proteins and polypeptides. Understanding the structural basis that regulates their formation may be important for the design of novel peptide-based molecules with a specific fold and stability. Here we report a statistical analysis of the relationships between secondary structure and disulfide bond formation, carried out using a large database of protein structures. Our analyses confirm the observation sporadically reported in previous investigations that cysteine residues located in alpha-helices display a limited tendency to form disulfide bridges. The very low occurrence of the disulfide bond in all alpha-chains compared to all beta-chains indicates that this property is also evident when proteins with different topologies are investigated. Taking advantage of the large database that endorsed the analysis on relatively rare motifs, we demonstrate that cysteine residues embedded in 3(10) helices present a good tendency to form disulfide bonds. This result is somewhat surprising since 3(10) helices are commonly assimilated into alpha-helices. A plausible structural explanation for the observed data has been derived combining analyses of disulfide bond sequence separation and of the length of the different secondary structure elements.
authors.affiliation: Dipartimento delle Scienze Biologiche, Sezione Biostrutture, and CNISM, Università degli Studi di Napoli Federico II, I-80134 Napoli, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: De Simone
authors.forename: Rita
authors.initials: R
authors.lastname: Berisio
authors.forename: Adriana
authors.initials: A
authors.lastname: Zagari
authors.forename: Luigi
authors.initials: L
authors.lastname: Vitagliano
mesh_terms: D003545:Cysteine / Q000737:chemistry; D030562:Databases, Protein / Q000706:statistics & numerical data; D004220:Disulfides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry
chemical_list: D004220:Disulfides; D011506:Proteins; D003545:Cysteine