Substrate Binding to Enzymes

Vladimir K Pliška, Swiss Federal Institute of Technology (ETH), Zürich, Switzerland

Published online: April 2001

DOI: 10.1038/npg.els.0000862

Binding of a substrate to an enzyme is the first step of the interaction between substrate (ligand) and enzyme molecules that leads to the formation of an intermediate substrate–enzyme complex. The formation process is controlled mainly by diffusion and requires a structural complementarity between the enzyme and ligand.

Keywords: substrate–enzyme complex; rate constants; dissociation constant; allosteric interactions; steady state; Michaelis constant; Hill equation; Adair equation; binding isotherm; weak bonds; hydrophobic interactions

Figure 1. Binding isotherms and linearized forms. (a) Direct plot of eqn (17) (Kd = 1, E0 = 1) for various values of the Hill coefficient η indicated on each curve. The same curves in the Scatchard plot (eqn (21)), double reciprocal plot (eqn (21)), and Scott plot (eqn (21)) are shown in (b), (c) and (d), respectively.
Figure 2. Binding isotherms of allosteric enzymes (according to Monod et al., 1965). (a) Effect of changing ‘microscopic’ constants in a homotropic system (eqn (19)). Values of κ are indicated on each curve. (b) Heterotropic system (eqn (20)). Heavy curve: homotropic system corresponding to the heavy curve in panel (a). Finely‐dashed curves show the effect of allosteric activators, and dashed curves those of allosteric inhibitors. For curves in both panels, KR = 103, n = 4.
Figure 3. Binding isotherm of the hyperbolic type (eqs. (2) and (5)): Error limits (dashed lines) of linearized binding data (according to Deranleau, 1969). (a) Semilogarithmic plot; (b) Lineweaver–Burk plot; (c) Scott plot. Values of intercepts (red arrows) and slopes in plots (b) and (c) are indicated.
close
 References
    Andrews PR, Craik DJ and Martin JL (1984) Functional group contributions to drug–receptor interactions. Journal of Medicinal Chemistry 27: 1648–1657.
    Atkins GL (1973) A simple digital‐computer program for estimating the parameters of the Hill equation. European Journal of Biochemistry 33: 175–180.
    Bundle DR and Sigurskjold BW (1994) Determination of accurate thermodynamics of binding by titration microcalorimetry. Methods in Enzymology 247: 288–305.
    Burgen ASV (1966) The drug–receptor complex. Journal of Pharmacy and Pharmacology 18: 137–149.
    Cooper PF and Wood GC (1968) Protein‐binding of small molecules: new gel filtration method. Journal of Pharmacy and Pharmacology 20: 150s–156s.
    Deranleau DA (1969) Theory of the measurement of weak molecular complexes. I. General considerations. Journal of American Chemical Society 91: 4044–4049.
    Hernández A and Ruiz MT (1998) An EXCEL template for calculation of enzyme kinetic parameters by non‐linear regression. Bioinformatics 14: 227–228.
    Fairclough GF and Fruton JS (1966) Peptide–protein interaction as studied by gel filtration. Biochemistry 5: 673–683.
    Monod J, Wyman J and Changeux J‐P (1965) On the nature of allosteric transitions: a plausible model. Journal of Molecular Biology 12: 88–118.
    Munson PJ (1983) LIGAND: a computerized analysis of ligand binding data. Methods in Enzymology 92: 543–576.
    Pliška V (1995) Multiple receptor populations: binding isotherms and their numerical analysis. Journal of Receptor and Signal Transduction Research 15: 651–675.
    book van Ginneken CAM (1977) "Kinetics of drug–receptor interaction". In: van Rossum JM (ed.) Kinetics of Drug Action, pp. 357–411. Berlin: Springer‐Verlag.
    Wieker H‐J, Johannes K‐J and Hess B (1970) A computer program for the determination of kinetic parameters from sigmoidal steady‐state kinetics. FEBS Letters 8: 178–185.
    Wilkinson GN (1961) Statistical estimations in enzyme kinetics. Biochemical Journal 80: 324–332.
 Further Reading
    book Kolev D (1998) Enzymology. London: World Scientific.
    book Price NC and Stevens L (1989) Fundamentals of Enzymology, 2nd edn. Oxford: Oxford University Press.
    book Segel IH (1993) Enzyme Kinetics. Behavior and Analysis of Rapid Equilibrium and Steady‐State Enzyme Systems. New York: Wiley.

Related Sub-Topics:

Biomolecular Interactions | Enzymes: Structure and Action Mechanism
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Substrate Binding to Enzymes
 
How to Cite close
Pliška, Vladimir K(Apr 2001) Substrate Binding to Enzymes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000862]