Influence of peptide dipoles and hydrogen bonds on reactive cysteine pKa values in fission yeast DJ-1.

ABSTRACT: Cysteine residues with depressed pK(a) values are critical for the functions of many proteins. Several types of interactions can stabilize cysteine thiolate anions, including hydrogen bonds between thiol(ate)s and nearby residues as well as electrostatic interactions involving charged residues or dipoles. Dipolar stabilization of thiolates by peptide groups has been suggested to play a particularly important role near the N-termini of α-helices. Using a combination of X-ray crystallography, site-directed mutagenesis and spectroscopic methods, we show that the reactive cysteine residue (Cys111) in Schizosaccharomyces pombe DJ-1 experiences a 0.6 unit depression of its thiol pK(a) as a consequence of a hydrogen bond donated by a threonine side chain (Thr114) to a nearby peptide carbonyl oxyg

SUBMITTER: Madzelan P 

PROVIDER: S-EPMC3484204 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature