Understanding the pKa of Redox Cysteines: The Key Role of Hydrogen Bonding

摘要: Abstract Many cellular functions involve cysteine chemistry via thiol–disulfide exchange pathways. The nucleophilic cysteines of the enzymes involved are activated as thiolate. A thiolate is much more reactive than a neutral thiol. Therefore, determining and understanding pKas functional important aspects biochemistry molecular biology with direct implications for redox signaling. Here, we describe experimental theoretical methods to determine pKa values, examine factors that control these pKas. Drawing largely on experience gained thioredoxin superfamily, roles solvation, charge–charge, helix macrodipole, hydrogen bonding interactions pKa-modulating factors. contributions in influencing associated chemistry, including relevance reaction kinetics thermodynamics, discussed. This analysis highlights critical role cystei...