Chirality in Biology
605
AC
R
B
b
ac
d
AC
S
B
c
a
b
d
D
d
a
A
C
b
c
R
D
d
a
A
C
b
c
S
L
D
W
X
COOH
NH
2
HO
OO
W
COOH
2
1
X
YZ
OH
(a)
(c)
(e)
(f)
(d)
(b)
Fig. 17
Models for chiral recognition. (a), (b) show the conventional Easson–Stedman
model for Cabcd (sequence assumed to be a
>
b
>
c
>
d). Three binding sites, A, B, and C,
are in a plane and it is assumed that the substrate (drug) cannot approach from below
(interior). Only the (
R
) enantiomer binds at all three sites, (a). (c), (d) diagram a modiFed
model with three binding sites, A, C, and D, in three dimensions. The substrate (drug) is
Cab(-CH
2
-c)d. Under these circumstances, both (
R
)and(
S
) enantiomers can bind at three
sites, (c), (d). A representation of mirror-image packing for phenylalanine enantiomers is
drawn at (e). ±or D-phenylalanine, W
=
H, X
=
CH
2
;for L-phenylalanine, W
=
CH
2
,X
=
H.
The aromatic rings (double bonds omitted) are drawn in the plane of the paper with NH
2
above and COOH below this plane. (f), Representation of mirror-image packing for
isocitrate enantiomers. ±or (1
R
,2
S
)-isocitrate, W
=
CH
2
,X
=
H, Y
=
OH, and Z
=
H. ±or
the (1
S
,2
R
) enantiomer, W
=
H, X
=
CH
2
,Y
=
H, and Z
=
OH. ±or both phenylalanine
and isocitrate, the CH
2
group provides a flexibility that makes the mirror-image packing
possible.
be either attractive or repulsive. In other
words, the minimal requirement is for a
four contact-point (four-point attachment)
model. In the Easson–Stedman model,
it was implicitly assumed that the drug
or enzyme substrate could approach the
protein surface only from above and not
from below, that is, from the ‘‘interior’’ of
the protein. Hence, this was a special case
of the four-point attachment model. There
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