Origin of the pKa perturbation of N-terminal cysteine in alpha- and 3(10)-helices: a computational DFT study.
It is well documented that helices in proteins can decrease the pKa of residues located at the N-terminus, but the real nature of this perturbation remains unclear. In the present work, the origin of the effect of 3(10)- and alpha-polyalanine helices on the pKa of an N-terminal cysteine residue is examined in gas phase as well as in aqueous solution by means of density functional theory. In a systematic study of the helix dipole, the proton affinity (PA), and the pKa of the N-terminal cysteine, in relation to both the helix length and the strength of the hydrogen bonds between the helix backbone amides and the Sgamma of the N-terminal cysteine, a direct relation between the terminal hydrogen bonds and the pKa perturbation is revealed.
Algemene Chemie (ALGC) and Departement Ultrastructuur, Vlaams Interuniversitair Instituut voor Biotechnologie (VIB), Vrije Universiteit Brussel (VUB), Pleinlaan 2, B-1050, Brussels, Belgium.
Goedele
G
Roos
Stefan
S
Loverix
Paul
P
Geerlings
D003545:Cysteine / Q000737:chemistry*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
D010455:Peptides; C019529:polyalanine; D003545:Cysteine