Harper's Illustrated Biochemistry, Volume 1 - Murray R. 1993

Structure and Function of Proteins and Enzymes
Enzymes: General Properties
"Three-Point Attachment" of Substrates to Enzymes

Most substrates form at least three bonds with an enzyme. Thanks to this "three-point attachment", a symmetrical molecule can exhibit Asymmetry. To illustrate this, let us imagine the substrate-binding region of an enzyme as a flat surface (although, as we shall soon see, the substrate-binding site of an enzyme is rarely flat, and perhaps never is). In Fig. 7.3, the substrate molecule is represented as a carbon atom with substituents, three of which interact with three points on the flat surface of the enzyme. If the substrate molecule can approach this site from only one side and only complementary structures of the substrate and enzyme can interact (both of which conditions are met in real Enzymes), then the substrate molecule can bind to the enzyme in only one way, even if groups 1 and 3 are identical. Mentally reviewing all possible spatial orientations of the substrate molecule, we can verify that the molecule can bind to the three points of the flat surface (from the same side) in only one orientation. It follows that groups 1 and 3, although identical, become nonequivalent upon binding to the enzyme due to differences in their microenvironment. Chemical changes will occur exclusively at group 1 and not at group 3 (or vice versa). Generalizing this reasoning, we can now explain why the enzymatic reduction of optically inactive Pyruvate yields specifically L-lactate rather than D, L-lactate.

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Fig. 7.2. NAD(P)⁺; R = H (in the case of NAD⁺) or -OPO^2-₃(in the case of NADP⁺).

Fig. 7.3. "Three-point attachment" of a substrate to a flat enzyme Active Site.