Organic Chemistry

1018 CHAPTER 24 Catalysis

CHCH 2

CH 2 CH 2

H 2 N

H 2 N

HN

N

H 2 N

C NHCHCO + H 2 O CO + H 3 NCHCO

+

NH 2

Arg 145

Tyr 248

Arg 127

NH

C

CO

O

Zn

Glu 270 C O

His 69 Glu 72

C

C

C

O

O

OH O

H

H

O

His 196

O O O O

O O

carboxypeptidase A

Overall Reaction

NH

N

CHCH 2

H 2 N

H 2 N

HN

N

H 2 N

NH 2

Arg 145

Tyr 248

Arg 127

NH

C

CO

O

Zn

Glu 270 C O

His 69 Glu 72

C

C

C

O

O

OH O

H

HO

His 196

NH

N

C

O

CHCH 2

H 2 N

H 2 N

H 2 N

NH 2

Arg 145

Tyr 248

Arg 127

NH 2

C

CO

O

HO

O

Zn

Glu 270 C

His 69 Glu 72

C

C

O

O

OH O

His 196

N

HN NH

N

C

O

CHCH 2

H 2 N

H 2 N

H 2 N

NH 2

Arg 145

Tyr 248

Arg 127

+NH 3

C

CO

O

O

O

Zn

Glu 270 C

His 69 Glu 72

C

C

O

O

OH O

His 196

N

HN NH

N

hydrophobic

pocket

− −

− − − −

− −

+ +

+ +

++

++

+

+

++

+

+

++

+

+

+

+

+ + + +

+ + + +

Figure 24.5

Proposed mechanism for the carboxypeptidase A–catalyzed hydrolysis of a peptide bond.

• In the second step of the reaction, Glu 270 functions as a general-acid catalyst,
  increasing the leaving tendency of the amino group. When the reaction is over,
  the amino acid (phenylalanine in this example) and the peptide with one less
  amino acid residue dissociate from the enzyme, and another molecule of

Tutorial:

Carboxypeptidase A

mechanism