Transition State Stabilization

Shahriar Mobashery, Wayne State University, Michigan, USA
Lakshmi P Kotra, Wayne State University, Michigan, USA

Published online: March 2002

DOI: 10.1038/npg.els.0000618

The transition state is a high-energy species occurring during the course of chemical reactions, the stabilization of which by either chemical reagents or enzymes enhances the rate of the given process.

Keywords: transition-state; inhibitor; deaminase; protease; Rubisco; drug design

Figure 1. (a) The energy profile for a hypothetical catalysed and an uncatalysed reaction. The TSUncat and ES‡ are transition state species for uncatalysed and enzyme-catalysed reactions, respectively, and G ‡ uncat and G ‡ cat refer to their corresponding free energy differences. G‡ is the stabilization energy of the enzyme–transition state complex. (b) Thermodynamic cycle depicting the two different possible pathways for arriving at the transition state species ES‡.
Figure 2. Several transition state species and their corresponding transition state analogues.
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 References
    Carlow D and Wolfenden R (1998) Substrate connectivity effects in the transition state for cytidine deaminase. Biochemistry 37: 11873–11878.
    Christensen H, Martin MT and Waley SG (1990) Beta-lactamases as fully efficient enzymes. Determination of all the rate constants in the acyl-enzyme mechanism. Biochemical Journal 266: 853–861.
    Christianson DW and Lipscomb WN (1985) Binding of a possible transition state analogue to the active site of carboxypeptidase A. Proceedings of the National Academy of Sciences of the USA 82: 6840–6844.
    Collins KD and Stark GR (1971) Aspartate transcarbamylase. Interaction with the transition state analogue N-(phosphonacetyl)-l-aspartate. Journal of Biological Chemistry 246: 6599–6605.
    Fersht AR, Shi JP, Wilkinson AJ et al. (1984) Analysis of enzyme structure and activity by protein engineering. Angewandte Chemie, International Edition, English 23: 467–473.
    Kim H and Lipscomb WN (1991) Comparison of the structures of three carboxypeptidase A–phosphonate complexes determined by X-ray crystallography. Biochemistry 30: 8171–8180, and references listed therein.
    Lolis E and Petsko GA (1990) Transition state analogues in protein crystallography: probes of the structural source of enzyme catalysis. Annual Reviews of Biochemistry 59: 597–630.
    Mader MM and Bartlett PA (1997) Binding energy and catalysis: the implications for transition-state analogs and catalytic antibodies. Chemical Reviews 97: 1281–1301.
    Martin JA (1992) Recent advances in the design of HIV proteinase inhibitors. Antiviral Research 17: 265–278.
    Page MI and Laws AP (1998) The mechanism of catalysis and the inhibition of -lactamases. Chemical Communictions 1609–1617.
    Persidis A (1997) Catalytic antibodies. Nature Biotechnology 15: 1313–1315, and references listed therein.
    Radzicka A and Wolfenden R (1995) Transition state and multisubstrate analog inhibitors. Methods in Enzymology 249: 284–312.
    Scheuring J and Schramm VL (1997) Kinetic isotope effect characterization of the transition state for oxidized nicotinamide adenine dinucleotide hydrolysis by pertussis toxin. Biochemistry 36: 4526–4534.
    Schramm VL (1998) Enzymatic transition states and transition state analog design. Annual Reviews of Biochemistry 67: 693–720.
    Wells TNC and Fersht AR (1985) Hydrogen bonding in enzymatic catalysis analysed by protein engineering. Nature 316: 656–657.
 Further Reading
    Cleland WW, Andrews TJ, Gutteridge S, Hartman FC and Lorimer GH (1998) Mechanism of Rubisco: the carbamate as a general base. Chemical Reviews 98: 549–561.
    book Fersht A (ed.) (1998) Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding. New York: WH Freeman.
    Morrison JF (1988) The behavior and significance of slow-binding inhibitors. Advances in Enzymology 61: 201–301.
    Ngo TT and Tunnicliff G (1981) Inhibition of enzymic reactions by transition state analogs: an approach for drug design. General Pharmacology 12: 129–131.
    Northrop DB (1981) The expression of isotope effects on enzyme-catalyzed reactions. Annual Reviews of Biochemistry 50: 103–131.
    Thomas NR (1994) Hapten design for the generation of catalytic antibodies. Applied Biochemistry and Biotechnology 47: 345–373.

Related Sub-Topics:

Biomolecular Interactions | Enzymes: Structure and Action Mechanism | Bioenergetics
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Article Title: Transition State Stabilization
 
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Mobashery, Shahriar, and Kotra, Lakshmi P(Mar 2002) Transition State Stabilization. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000618]