Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

Enzymes are Wonderful Catalysts 39
pK a 3 4 5 6 7 8 9 10 11
Asp/Glu
His
Cys
Lys
Tyr
= ‘normal’ range of pK a values
= unusual pK a values observed in specific cases
Figure 3.12 Range of pK a values observed for amino acid side chains in enzyme active sites.
+ deprotonated at pH 7;
pK a reduced by adjacent positive charge
NH 3
O
NH 2
O
+
H 3 N
NH 2
N
H
N
H
deprotonated at pH 7.5-10
(pK 1 = 10.7, pK 2 = 7.5)
Figure 3.13 Abnormally low lysine pK a in acetoacetate decarboxylase.
Similarly, if a charged group was involved in a salt bridge with an oppositely
charged residue, its pK a would be altered, or if it was in a hydrophobic region
of the active site, which would destabilise the charged form of the group. So, for
example, we shall later on see protonated aspartic acid and glutamic acid
residues acting as acidic groups in some cases (i.e. with elevated pK a values of
7.0 or above). Finally, it is worth noting that histidine, whose side chain
contains an imidazole ring of pK a 6–8, can act either as an acidic or a basic
residue, depending on its particular local pK a , making it a versatile reagent for
enzymatic acid/base chemistry.
Acid/base catalysis by enzymes is made that much more eVective by the
optimal positioning of the active site acid/base groups in close proximity to
the substrate, generating a high eVective concentration of the enzyme reagent.
This can be illustrated in the case of glycoside hydrolysis using the data from
Figure 3.1. The mechanism of the non-enzymatic reaction involves protonation
of the glycosidic group by external acid to form a good leaving group, followed
by formation of an oxonium intermediate. Glycoside hydrolysis can be accelerated
dramatically by positioning an acidic group in close proximity to the
glycosidic leaving group, as shown in Figure 3.1. Enzymes which catalyse