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.
Roos
Goedele
G
Algemene Chemie (ALGC) and Departement Ultrastructuur, Vlaams Interuniversitair Instituut voor Biotechnologie (VIB), Vrije Universiteit Brussel (VUB), Pleinlaan 2, B-1050, Brussels, Belgium.
Loverix
Stefan
S
Geerlings
Paul
P
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