Organic Chemistry

Section 24.9 Enzyme-Catalyzed Reactions 1023

CH 2

CH 2 OH

Trp

62

Trp

63

C 107

H

H

H

O

O

O

H

O

RO

O

O

O

H

H 2 N

NH

H 2 N

C

H N

CH 2

Asp 101

O

O

H

RO

O

O

OH

HO CH 2 OH

CH 3

A

B

NAG

NAM

CNAG

DNAM

NAG

F NAM

N

H

H

O

C

C

O

−O

O

RO CH 2

H

H 2 N

O

O

O

NH 2

Asn NH 2

44

Arg

114

Asn

37

Gln

(^57) O H
O
O
O
O CH 2 OH
59 N H
O C 57
O C 34
35 C O
N
O CH 3
C
CH 3 N
H
O
C
CH 3 N
H
O
C
CH 3 N
H
O
C
C
O
C
CH 3
O C N N + +
E
lysozyme cleavage

Figure 24.8
The amino acids at the active site
of lysozyme that are involved in
binding the substrate.
and a better leaving group. Site-specific mutagenesis studies show that when
Glu 35 is replaced by Asp, the enzyme has only weak activity. Apparently, Asp
does not have the optimal distance and angle to the oxygen atom that needs to be
protonated. When Glu 35 is replaced by Ala, an amino acid that cannot act as an
acid catalyst, the activity of the enzyme is completely lost.

• In the second step of the reaction, Glu 35 acts as a general-base catalyst to
  increase water’s nucleophilicity. The configuration at C-1 of the NAM residue is
  retained because the enzyme shields one side of the intermediate, so water is
  able to attack from only one side.

3-D Molecule:

Lysozyme with bound NAG 4