title: Conformational preferences and pK(a) value of selenocysteine residue.
abstract: The conformational preferences of the L-selenocysteine (Sec) dipeptides with selenol and selenolate groups (Ac-Sec-NHMe and Ac-Sec(-) -NHMe, respectively) and the apparent (i.e., macroscopic) pK(a) value of the Sec residue have been studied using the dispersion-corrected density functionals M06-2X and B2PLYP-D with the implicit solvation method in the gas phase and in water. In the gas phase, the backbone-to-backbone and/or side chain-to-backbone hydrogen bonds are found to contribute in stabilizing the most preferred conformations for the Sec and Sec(-) residues, as seen for the Cys and Cys(-) residues. However, the polyproline II-like conformations prevail over the conformations with the backbone-to-backbone hydrogen bonds in water because of the weakened hydrogen bonds by the favorable direct interactions between the backbone CO and HN groups and water molecules. The Sec and Sec(-) residues are found to adopt more various conformations than the Cys and Cys(-) residues in water, although the most preferred conformations of the neutral and/or anionic forms of the two residues are similar each other in the gas phase and in water. Using the statistically weighted free energies of the Sec and Sec(-) dipeptides in the gas phase and their solvation free energies, the pK(a) value of the Sec residue is estimated to be 5.47 at 25°C, which is in good agreement with the experimental value of 5.43 ± 0.02. It is found that the lower pK(a) value of the selenol side chain for the Sec residue by ∼3 units than the thiol side chain for the Cys residue is ascribed to the higher gas-phase acidity of the Sec residue.
authors.affiliation: Department of Chemistry, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Byung Jin
authors.initials: BJ
authors.lastname: Byun
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Kang
mesh_terms: D004151:Dipeptides / Q000737:chemistry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D044367:Phase Transition; D011487:Protein Conformation; D017279:Selenocysteine / Q000737:chemistry*; D051140:Selenoproteins / Q000737:chemistry*; D012997:Solvents; D013816:Thermodynamics
chemical_list: D004151:Dipeptides; D051140:Selenoproteins; D012997:Solvents; D017279:Selenocysteine