New enzyme theory rewrites catalysis

Related tags Chemical reaction Enzyme

Scientists have reworked the mechanism of how enzymes work, forcing
the pharmaceutical industry to rethink its views on the design of
biological catalysts and new drugs.

The discovery may explain why attempts to make artificial enzymes have been disappointing and could provide a stepping stone to the introduction of next generation drugs that take this discovery to produce drugs with improved efficacy.

The new breakthrough could revolutionise the application of enzymes, which are vital for catalysis within industry. Enzymes are biological molecules that accelerate chemical reactions and are central to the existence of life.

The discovery centres on a new phenomenon occurring at the same atomic level that dictates how enzymes work and reveals that chemical reactions can proceed through energy barriers. This is contrary to received wisdom on how enzyme reactions work.

Professors Nigel Scrutton of the Department of Biochemistry at The University of Leicester said: "Since the discovery of enzymes just over a century ago, we have witnessed an explosion in our understanding of enzyme catalysis, leading to a more detailed appreciation of how they work."

"However, despite the huge efforts to redesign enzyme molecules for specific applications (e.g. the synthesis of fine chemicals, food processing, bio sensing, brewing), progress in this area has been generally disappointing. This stems from our limited understanding of the subtleties by which enzymes enhance reaction rates."

Working alongside Scrutton, Prof Mike Sutcliffe, Department of Biochemistry at the University of Leicester, told In-Pharmatechnologist.com​: "We are referring to enzymes that achieve fast reaction rates for the breaking of stable carbon-hydrogen bonds (e.g. oxidation of stable substrates)."

"The textbook explanation is the more energy required to break the bond, the slower the reaction. This results from a higher (energy) barrier for the reaction. However, the invoking of quantum mechanical tunneling through the barrier explains this apparent paradox."

The team, from The University of Leicester,​ have demonstrated this occurs in enzyme-catalysed reactions, and their studies revealed that carbon-hydrogen bond breakage occurs by the hydrogen passing through, rather than over, the barrier. This is a quantum mechanical effect. The hydrogen passes instantaneously from one side of the barrier to the other. In these tunneling reactions, the rate of reaction depends on both the height and width of the barrier.

"Since electron and hydrogen transfer is common to virtually all naturally occurring enzymes, the discovery has wide ranging implications for our understanding of how enzymes work,"​ added Sutcliffe.

The discovery has raises questions on the use of enzymes in industry and biomedical research, as the new theory is likely to underpin the mode of action of all enzymes.

Sutcliffe said: "In cases where enzymes that break stable bonds are being targeted, it may well no longer be valid to assume that effective inhibitors of these enzymes can be designed solely by considering the binding of a transition state analogue to block the active site."

"For example, the new discovery questions current approaches used to rationally design enzyme inhibitors for the production of pharmaceuticals or novel enzyme catalysts for industrial applications,"​ Scrutton added.

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