198 Topics in Current Chemistry Editorial Board: A. de Meijere KN ...

42 J.P. Glusker
Fig. 34. Glycine crystals binding optically active amino acids [86, 116]. Shown is the binding of
D-alanine to the 010 face and L-alanine to the 01 – 0 face. The methyl groups of alanine are
stippled circles for the former, and filled circles for the latter
9
Applications to Macromolecular Structures
Macromolecular recognition often involves many points of interaction, whether
it is subunit assembly, substrate or inhibitor binding or the operation of control
factors. The binding of drugs to biological macromolecules involves a fit between
the drug and its receptor that depends not only on their respective shapes,
but also on the distribution of electronic charge on the surfaces of both molecules
so that a complementary fit may be obtained. Molecules with similar, but
not identical, formulae may bind to the same receptor in the same or different
ways, depending on the nature of the functional groups in each.
9.1
Binding of Drugs to Dihydrofolate Reductase
An extensively studied enzyme-inhibitor system involves the protein dihydrofolate
reductase [88]. Crystallographic results demonstrate an important feature
of drug-enzyme interactions; an inhibitor drug may not bind in the same way as
substrate even though both have similar chemical formulae. This enzyme catalyzes
the reduction of 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate, an essential