Allemann group research is published in PNAS
02 Hydref 2013
Mae'r cynnwys hwn ar gael yn Saesneg yn unig.
Researchers from Cardiff University's School of Chemistry, along with colleagues from the University of Bristol, the University of València and Jaume I University in Castelló, have uncovered a mechanism by which enzyme motions couple to chemical reactions.
Enzymes are fundamental to life. They are proteins that catalyse chemical reactions, often increasing reaction rates by several trillion times. They find uses in industries such as food, cosmetics, detergents, pharmaceuticals and chemical manufacturing. Several theories have been developed to explain the enormous catalytic power of enzymes, but even after a century of study this is not fully understood. Some theories propose that internal 'promoting motions' of the enzyme, specific motions that act to reduce the height or width of the energy barrier to the reaction, are used to drive the chemistry. This remains a topic of considerable debate, particularly since the identification and analysis of dynamical effects in enzyme-catalyzed reactions has proven very challenging.
The team, led by Professor Rudolf Allemann, used a combination of experimental and computational approaches to study the enzyme dihydrofolate reductase, an important target for anti-infective and anti-cancer drugs. Their work, published* in the journal Proceedings of the National Academy of Sciences of the U.S.A., involved complete substitution of the enzyme's hydrogen, carbon and nitrogen atoms with their heavier isotopes. This alters the enzyme's motions on a wide range of timescales, but not its chemical properties. They found no significant role for 'promoting motions' in the reaction, but did demonstrate coupling of enzyme motions to the catalysed reaction on a femtosecond timescale (one millionth of a billionth of a second). Enzyme dynamics therefore have a small, but measurable, effect on the chemical reaction rate.
Professor Allemann said: "This is a leap forward in our understanding of enzyme catalysis. It shows that 'promoting motions' are not, after all, required to explain rate enhancements, but shows that enzyme motions are involved in the reaction through a passive rather than an active mechanism".
This work significantly advances our fundamental understanding of enzyme catalysis. A thorough understanding of how enzymes achieve their phenomenal rate enhancements is of great importance to fields like biocatalysis, bioenergy, drug design, and the emerging field of synthetic biology.