ABSTRACT
Cysteine is usually the most powerful nucleophile in a protein and, as a result, is frequently the easiest to selectively modify with a variety of reagents. Cysteine is the sulfur analogue of serine in which the hydroxyl group is replaced with a sulfhydryl group. The reader is directed to an excellent review of thiols
for a more thorough discussion of both aliphatic and aromatic thiols. The bond dissociation energy for sulfhydryl groups is substantially less than that for the corresponding alcohol function, providing a basis for the increased acidity of sulfhydryl groups; for example, the p
K
for ethanethiol is 10.6 whereas it is 18 for ethanol. As a consequence, the reaction of cysteine with chloroacetate is slow (5.3
×
M
min
) whereas that with serine is nonexistent; the reaction of a cysteine residue at an enzyme active site (papain) is ca. 30,000 times faster (150
M
min
) than that of free cysteine at pH 6.0.
