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Allosteric regulation and catalysis emerge via a common route

Nature Chemical Biology volume 4, pages 474–482 (2008)Cite this article

Abstract

Allosteric regulation of protein function is a mechanism by which an event in one place of a protein structure causes an effect at another site, much like the behavior of a telecommunications network in which a collection of transmitters, receivers and transceivers communicate with each other across long distances. For example, ligand binding or an amino acid mutation at an allosteric site can alter enzymatic activity or binding affinity in a distal region such as the active site or a second binding site. The mechanism of this site-to-site communication is of great interest, especially since allosteric effects must be considered in drug design and protein engineering. In this review, conformational mobility as the common route between allosteric regulation and catalysis is discussed. We summarize recent experimental data and the resulting insights into allostery within proteins, and we discuss the nature of future studies and the new applications that may result from increased understanding of this regulatory mechanism.

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Figure 1
Figure 2: Different modes of allosteric behavior.
Figure 3: The kinetic pathway of DHFR catalysis shown together with DHFR conformational ensembles identified by NMR relaxation dispersion measurements.
Figure 4: Changing ensembles of protein conformation are manifested in catalysis and allostery.
Figure 5: Signal transduction network for TonB-dependent transporters.
Figure 6: Summary of the overall effect of binding of cAMP on the dynamics of CAP at various timescales.
Figure 7: The crystal structure of a tumor suppressor protein complex.

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Acknowledgements

We thank S. Hammes-Schiffer for helpful discussions.

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  1. Department of Chemistry and Biochemistry, Montclair State University, 1 Normal Avenue, Montclair, 07043, New Jersey, USA

    Nina M Goodey

  2. Department of Chemistry, The Pennsylvania State University, 414 Wartik Laboratory, College Park, 16802, Pennsylvania, USA

    Stephen J Benkovic

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Correspondence to Stephen J Benkovic.

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Goodey, N., Benkovic, S. Allosteric regulation and catalysis emerge via a common route. Nat Chem Biol 4, 474–482 (2008). https://doi.org/10.1038/nchembio.98

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