Binding and Catalysis


Binding and catalysis in the biological context are defined as the formation of a relatively long‐lived and specific complex between a macromolecular catalyst and a substrate molecule, which subsequently undergoes a chemical transformation much faster than would occur in the absence of the macromolecular catalyst.

Keywords: entropy loss; induced fit; stereoelectronic effects; ground state destabilization; transition state stabilization; circe effect

Figure 1.

Aldimine formed between an α‐amino acid and pyridoxal phosphate. The p orbitals of the conjugated aldimine/pyridine ring π system are shown, as is the sp3 orbital of the Cα–CO2 bond. The latter is orientated such that maximal stereoelectronic effects will be gained in the transition state for decarboxylation. As the Cα–CO2 bond breaks, the nascent p orbital will be maximally aligned with the p orbitals of the aldimine/pyridine ring π system, thereby maximally stabilizing the carbanionic character at Cα. Binding interactions between enzyme active sites and the aldimine maintain the optimal conformation.

Figure 2.

Schematic of the free energy changes that occur in a simplified enzymatic reaction. The energy levels have been offset from zero for clarity. The substrate self‐energy is the electronic energy of the substrate that would be found if it were transferred to the gas phase. The enzyme–substrate interaction energy is the binding energy between enzyme and substrate. Formation of either the E‐S or E‐P complexes occurs with a small decrease (favourable change) in enzyme–substrate interaction energy. On going from the E‐S or E‐P complexes to the transition state for the chemical interconversion, the enzyme–substrate interaction energy decreases by a large amount, indicating selective transition state stabilization. The substrate self‐energy does not change on binding to the enzyme (in the absence of ground state destabilization). It undergoes a large increase on going from either the E‐S or E‐P ground states to the transition state owing to the electronic structure changes that are entailed in the process. The net result is the observed energy profile, which is the sum of the profiles for the substrate self‐energy and the enzyme–substrate interaction energy. It decreases slightly on substrate binding, and increases in the chemical step since the magnitude of the change in the substrate self‐energy is larger than that of the enzyme–substrate interaction energy. The barrier in the substrate self‐energy is invariant. Thus, selective transition state binding will always increase the catalytic rate constant.

Figure 3.

Schematic of ground and transition state interactions made in tyrosyl‐tRNA synthetase. The γ‐phosphate does not interact with Thr40 and His45 in the ground state. The change in the geometry at the α‐phosphate in the transition state allows the γ‐phosphate to make hydrogen bonds to Thr40 and His45 selectively in the transition state.



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Further Reading

Jencks WP (1975) Binding energy, specificity, and enzymic catalysis: the circe effect. Advances in Enzymology and Related Areas of Molecular Biology 43: 219–410.

Jencks WP (1969) Catalysis in Chemistry and Enzymology. New York: McGraw‐Hill.

Cornish‐Bowden A (1995) Fundamentals of Enzyme Kinetics. London: Portland Press.

Fersht A (1985) Enzyme Structure and Mechanism. New York: Freeman.

This article was reviewed by the editors in 2013 and was found to still be up to date.

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Toney, Michael D(Apr 2001) Binding and Catalysis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0000629]