SECTION 25.10
Protein Synthesis
583
a
H
3
C x /
C H
3
H ,C V
T )H
C O N H ,
O H
O
O H
O
T e tr a c y c lin e : In h ib its th e b in d in g o f
a m in o a c y l tR N A s to th e rib o s o m e in
b a c te ria .
O H
O H
S tr e p t o m y c in : In te rfe re s w ith p a irin g b e tw e e n
a m in o a c y l tR N A s a n d R N A c o d o n s , c a u s in g
m is re a d in g .
E r y th r o m y c in : B in d s to a s p e c ific
s ite o n th e 2 3 S R N A a n d b lo c k s
e lo n g a tio n b y in te rferin g w ith th e
tra n s lo c a tio n s te p .
d
C H C lj
C h lo r a m p h e n ic o l : B lo ck s e lo n g a tio n ,
a p p a r e n tly by a c tin g a s a c o m p e titiv e
in h ib ito r for th e p e p tid y ltra n s fe ra s e c o m
plex . T h e a m id e link ( r e d ) re s e m b le s
a p e p tid e b o n d .
F I G U R E 2 5 - 1 8
Antibiotic inhibitors of protein synthesis.
e
H3cx ^CHj
N
P u r o m y c in : C a u s e s p r e m a tu r e c h a in te rm in a tio n .
T h e m o le c u le r e s e m b le s th e 3 ' e n d o f th e a m in o -
a c y la te d tR N A a n d will e n te r th e A s ite . It tr a n s f e r s
to th e g ro w in g c h a in c a u s in g p r e m a tu r e te rm in a tio n .
emphysema. Prenatal diagnosis of
a
i -AT can be done by
the use of either synthetic oligonucleotide probes or re-
striction fragment length polymorphism analysis.
The reactive site of
a
i - AT is at the methionine residue,
position 358. The sequence around the reactive center of
several proteinase inhibitors, including
a \
-AT, antithrom-
bin III, and several unrelated plant proteinase inhibitors,
is strikingly similar. In fact,
a
i -AT, antithrombin III, and
ovalbumin (a protein without known inhibitory function)
share extensive homologies and may all have evolved from
a common ancestral protease inhibitor more than 500 mil-
lion years ago. A fatal bleeding disorder due to substitu-
tion of a methionine for an arginine residue at position
358 of
a\
-AT has been reported. This particular alteration
brought a change in the specificity of the inhibitor. This
altered protein (known as
a \
-antitrypsin Pittsburgh) ex-
hibits antithrombin activity while losing antielastase ac-
tivity. Antithrombin III, which has an important regulatory
