The Origins of Enzyme Catalysis and Reactivity: Further Assessments
Asian Journal of Chemical Sciences,
Alternatives to conventional mechanisms of enzyme catalyzed reactions, although within the ambit of transition state theory, are explored herein. This is driven by reports of a growing number of enzymes forming covalently linked enzyme-substrate intermediates, which clearly deviate from the conventional Michaelis-complex mechanism. It is argued that the formation of the covalent intermediates can be accommodated within the framework of transition state theory and the original Pauling hypothesis. This also obviates the need to invoke intramolecular reactivity to explain enzymic accelerations. Thus, the covalent binding of a substrate distorted towards the transition state, with the binding being fully manifested in the ensuing transition state, would conform to the traditional endergonic pre-equilibrium mechanism. Intriguingly, an alternative exergonic formation of the covalent intermediate would also lead to catalysis: in this case, any of the three steps–covalent binding, turnover or product release–can be rate limiting. Although the exergonic mode has been dismissed previously as leading to a “thermodynamic pit” (Michaelis complex case), this view now needs to be reassessed as it seems inaccurate. Therefore, it remains for the enzyme to stabilize the various transition states via the multifarious mechanisms available to it. The Pauling hypothesis remains vindicated.
- Covalent linking
- enzyme-substrate intermediate
- pauling hypothesis
- transition state stabilization
How to Cite
Chandrasekhar, S. Understanding enzymic reactivity–new directions and approach- es. Asian Journal of Research in Biochemistry. 2020;7(2):1-13.
Agarwal PK. A biophysical perspective on enzyme catalysis. Biochemistry. 2019;58 (6):438–449.
Fersht A. Structure and mechanism in protein science. 2nd ed. Cambridge (UK): Kaissa Publications; 2017.
Kirby AJ, Hollfelder F. From enzyme models to model enzymes. Cambridge (UK): Royal Society of Chemistry; 2009.
Zhang X, Houk KN. Why enzymes are proficient catalysts: beyond the Pauling paradigm. Acc Chem Res. 2005:38(5):379-385.
Silverman RB. The organic chemistry of enzyme-catalyzed reactions. San Diego: Academic Press; 2002.
Chandrasekhar S. Intramolecularity and enzyme modelling: A critique. Res Chem Intermediat. 2003;29(1):107-123.
Chandrasekhar S. Reformulation of activated complex theory. viXra e-print archive; 2012.
Steinfeld JL, Francisco JS, Hase WL. Chemical kinetics and dynamics. 2nd ed. Upper Saddle River: Prentice Hall; 1999.
Chandrasekhar S. On the presumed kinetic consequences of pre-equilibrium. Implications for the Michaelis-Menten equation. Zh Fiz Khim A. 2012;86(4):709-713.
Huang Y, Bolen DW. Covalent bond changes as a driving force in enzyme catalysis. Biochemistry. 1993;32(36):9329-9339.
Bruice TC, Bruice PY. Covalent intermediates and enzyme proficiency. J Am Chem Soc. 2005;127(36):12478-12479.
Imamura K, Matsuura T, Nakagawa A, Kitamura S, Kusunoki M, Takaha T, et al. Structural analysis and reaction mechanism of the disproportionating enzyme (D-enzyme) from potato. Protein Science. 2020;29(10):2085-2100.
Klimacek M, Sigg A, Nidetzky B. On the donor substrate dependence of group-tra nsfer reactions by hydrolytic enzymes: Insight from kinetic analysis of sucrose phosphorylase-catalyzed transglycosyla- tion. Biotechnology and Bioengineering. 2020;117(10):2933-2943.
Das D, Kuzmic P, Imperiali B. Analysis of a dual domain phosphoglycosyl transferase reveals a ping-pong mechanism with a covalent enzyme intermediate. Proc Natl Acad Sci USA. 2017;114(27):7019-7024. DOI: doi.org/10.1073/pnas.1703397114.
Holland MC, Gilmour R. Deconstruct- ing covalent organocatalysis. Angew Chem Int Ed. 2015;54(13):3862-3871.
Luedtke S, Neumann P, Erixon KM, Leeper F, Kluger R, Ficner R, Tittmann K. Sub-angstrøm-resolution crystallography reveals physical distortions that enhance reactivity of a covalent enzymatic Inter- mediate. Nature Chemistry. 2013;5(9):762-767. DOI: doi.org/10.1038/nchem.1728.
Jancewicz LJ, Wheatley RW, Sutendra G, Lee M, Fraser ME, Huber RE. Ser-796 of β-galactosidase (Escherichia coli) plays a key role in maintaining a balance between the opened and closed conformations of the catalytically important active site loop. Archives of Biochemistry and Biophysics. 2012;517(2):111-122.
Sobala LF, Speciale G, Zhu S, Raich L, Sannikova N, Thompson AJ, et al. An epoxide intermediate in glycosidase catalysis. ACS Central Science. 2020;6(5):760-770.
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