Enzyme Activity: Allosteric Regulation

Thomas Traut, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA

Published online: September 2007

DOI: 10.1002/9780470015902.a0000865.pub2

Cells can respond to changes in their environment by altering the flow through particular metabolic pathways. Such a change in any metabolic step is due to certain key enzymes that have the ability to alter their rate of activity. Such enzymes are defined as allosteric. The extent to which these enzymes adopt either the active conformation or the inactive conformation depends on their response to appropriate positive or negative signals. An easily measured feature of allosteric enzymes is the cooperativity that they show in a kinetic experiment.

Keywords: allosteric; conformation; enzyme; negative cooperativity; positive cooperativity; regulation

Figure 1. Sigmoidal kinetics define an allosteric enzyme with positive cooperativity. The dashed lines indicate the concentration of substrate at which the enzyme has 50% of the maximum activity (Vmax). (a) Normal enzyme (no cooperativity); (b) allosteric enzyme (cooperative kinetics).
Figure 2. Energetics and equilibria for the two enzyme conformations. Abbreviations: T, inactive conformation; R, active conformation; A, activator; I, inhibitor; S, substrate. (a) and (b) depict a system where the T conformation is more stable, while in (c) and (d) the R conformation is more stable.
Figure 3. Frequency of active and inactive conformations for (a) normal enzymes and (b) allosteric enzymes. The upper horizontal line denotes Vmax.
Figure 4. Examples of (a) no cooperativity, (b) positive cooperativity and (c) negative cooperativity. The upper horizontal line denotes Vmax. Dashed lines indicate 50% binding and this defines Km or K0.5.
Figure 5. A simple ligand binding curve: the binding of H+ by acetate anion. (a) Semilog plot and (b) linear plot.
Figure 6. The correlation between change in affinity and change in maximum activity for V-type enzymes.
Figure 7. Models for cooperativity in the binding of oxygen by haemoglobin. (a) Concerted or symmetry model and (b) sequential or induced fit model.
Figure 8. Graphic plots for analysing enzyme kinetics. For each of the four types of graphic analysis, panel (a) is for noncooperativity; panel (b), positive cooperativity and panel (c), negative cooperativity. In the Hill plots, the red dashed line has a slope of 1.0. The blue dashed lines indicate the affinity for substrate.
Figure 9. Structure of phosphofructokinase from B. stearothermophilus. The enzyme is a tetramer and each subunit has two domains. The two substrates, fructose 6-phosphate (F6P) and ATP define the catalytic site. Two alternate effectors bind at the same regulatory site. Note that the binding of F6P, and also of the effectors, is between subunits.
Figure 10. Catalytic site of phosphofructokinase. The solid line represents the backbone of the polypeptide chain, dashed lines in red represent non-covalent bonds. The bold dashed line is the interface between subunit 1 and subunit 2 of Figure 9. (a) T conformation in the absence of ligands and (b) R conformation when F6P and ADP are at the catalytic site. Amino acids 155–162 form the 6F loop. Adapted from Schirmer and Evans 1990.
Figure 11. Allosteric regulation as a function of regulatory effectors and available substrate concentration. Arrows on the abscissa indicate (a) the concentration of substrate equal to Kmand (b) a constant concentration of substrate in the cell.
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 References
    Choe J-Y, Poland BW, Fromm HJ et al. (1998) Role of a dynamic loop in cation activation and allosteric regulation of recombinant porcine fructose-1,6-bisphosphatase. Biochemistry 37: 11441–11450.
    Koshland DE Jr, Némethy G and Filmer D (1966) Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry 5: 365–385.
    Levitzki A and Koshland DE Jr (1969) Negative cooperativity in regulatory enzymes. Proceedings of the National Academy of Sciences of the USA 62: 1121–1128.
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    Schirmer T and Evans PR (1990) Structural basis of the allosteric behaviour of phosphofructokinase. Nature 343: 140–145.
    book Traut T (2008) Allosteric Regulatory Enzymes, p. 198. New York: Springer.
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 Further Reading
    book Perutz M (1990) Mechanisms of Cooperativity and Allosteric Regulation in Proteins. New York: Cambridge University Press.

Related Sub-Topics:

Intracellular and Extracellular Signalling | Protein Structure | Proteins: Structure, Function, Metabolism | Enzymes: Structure and Action Mechanism
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Article Title: Enzyme Activity: Allosteric Regulation
 
How to Cite close
Traut, Thomas(Sep 2007) Enzyme Activity: Allosteric Regulation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000865.pub2]