To determine the accessibility of cysteines in purified PHLPP2, we assessed their reactivity with iodoacetamide under native conditions. After denaturing with urea and reducing potential disulfide bridges with TCEP, the remaining free cysteines were modified with methyl methanethiosulfonate. This 2-step differential alkylation experiment was compared to the 1-step alkylation reactions under fully denaturing conditions with iodoacetamide and methyl methanethiosulfonate.