Chemistry Reference
In-Depth Information
6
Artificial Hydrolytic Metalloenzymes
Jik Chin and Hae-Jo Kim
6.1
Introduction
Hydrolytic metalloenzymes [1-3] play many important roles in life. Proteases, phos-
pholipases and nucleases that hydrolyze proteins, lipids and nucleic acids often re-
quire one or more metal ions. Metalloenzymes that hydrolyze phosphoproteins
play important roles in signal transduction [4-7]. Enzymes that make DNA by trans-
esterification such as polymerases [8] and reverse transcriptases [9] are activated by two
metal ions. In addition, many RNA enzymes that catalyze transesterification and
hydrolysis reactions are activated by more than one metal ion [10]. Over the years,
there has been considerable interest in understanding the role of metal ions in these
important biological reactions. Much has been learned through elegant designs and
careful analyses of simple metalloenzyme models [11-15]. These studies provide valu-
able information on how some of these enzymes provide enormous rate-accelerations
for the hydrolysis reactions. Furthermore, the knowledge gained from such studies
may provide interesting insights into designing metal complexes that catalyze not
only hydrolysis reactions but also a wide variety of organic reactions. In This chapter
presents some of the fundamental roles that metal ions play in hydrolyzing esters,
amides, nitriles and phosphate esters.
6.2
Reactivity of Substrates
To understand the role of metal ions in hydrolysis reactions, it is useful to first con-
sider the 'background' hydrolysis reactions. Table 6.1 lists the second-order rate con-
stants for hydroxide-catalyzed hydrolysis of various substrates. The reactivity of methyl
acetate (first entry in Table 6.1) [16] is comparable to those of other unactivated esters
found in nature (e.g. acetyl choline and carboxyl esters in phospholipids). The reac-
tivity of N-methylacetamide (second entry in Table 6.1) [17] is comparable to those of
typical peptides (1.1
10
-6
M
-1
s
-1
) [18] and that of dimethyl phosphate (P-O bond
