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Im
O
Zn +2
+
Im
O
C
Im
H
O
Im
O
Zn +2
Im
O
C
O -
Im
H
H 2 O
Im
O
+ H +
Zn +2
+ H
Im
O
O
C
O -
Im
H
Im = imidazole
FIGURE 12.4
The main features of the mechanism of carbonic anhydrase.
His 142
HN
HN
His 69
HN
His 69
N
N
N
O
O
O
Zn II
Zn II
Zn II
OH 2
Glu 72
OH 2
OH 2
Glu 165
Glu 72
O
O
O
N
N
N
HN
HN
His 196
HN
His 196
His 146
thermolysin
carboxypeptidase A
carboxypeptidase B
FIGURE 12.5
Active sites of thermolysin and carboxypeptidases A and B.
Bovine carboxypeptidase A was only the third protein, after myoglobin and lysozyme, to have its three-
dimensional structure solved at high resolution. The active site zinc is bound to His-69, Glu-72, and His-196
( Figure 12.5 ), and to a water molecule. The zinc-bound water molecule is itself hydrogen bonded to Glu-270.
Despite extensive experimental data, the mechanism of carboxypeptidase still remains controversial. Two major
 
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