Research Groups
Introduction
Blundell Brindle Broadhurst Brown Carrington Dupree Evan  Head of Dept. Farndale Gay Grace Griffin Hendrich Hesketh Higgins Hollfelder Hong Howe Hyvonen Jackson S Jackson T Jackson R Laue Leadlay Lester Lilley Lipkow	Livesey Luisi Lummis Mata McCafferty Metcalfe Mishima Miska Monie Mott Murzina Nietlispach Owen Oliver Packman Pellegrini Robinson Salmond Scadden Silva Smith A Smith C Standart Thomas Timmers Tolkovsky Welch Zhang
Past members

Visit Hollfelder group web site

Mechanisms in Chemistry and Biology

Research Groupings: Structural and molecular cell biology | Functional genomics, systems biology and genetic medicine

Enzymes define the chemistry of life and have evolved to perform biological tasks with exquisite specificity and amazingly efficiently – biomolecules are processed in second by enzyme, although their reactivity may be about a million years. This tremendous power of enzymes corresponds to huge rate accelerations of over 10²¹! Despite much progress we still have no comprehensive understanding of enzyme action. In particular, we do not understand how enzymes bring about catalysis. So first we study enzymes to delineate their mechanisms But our understanding certainly fails the most severe test: that of making enzymes rivalling the efficiency of natural catalysts. A fundamental understanding of the principles responsible for enzyme efficiency may enable us in the future to describe, manipulate and ultimately make biocatalysts. We hope that we can extend the lessons learned to potential applications in sophisticated synthetic chemistry, biotechnology and medicine.

Enzyme-substrate interactions in the transition state. The nature, magnitude and arrangement of these stabilising interactions indicated by red arrows are the focus of this research

We can now tackle the enigma of bio-catalysis using a variety of interdisciplinary approaches (often pursued in collaboration with groups in the UK, Switzerland, Israel, Germany and in a European Network on Directed Evolution. Our thinking remains chemical, but we use techniques taken from molecular biology and protein chemistry to biophysics as well as mechanistic organic chemistry. We study natural enzymes to learn how nature has solved a catalytic problem, we make artificial enzyme-like models ('plastic enzymes'), we recruit existing proteins for new tasks (‘promiscuous’ and 'off-the-peg' proteins), look at the uncatalysed reactions to understand the intrinsic bond making and breaking process involved and select catalysts from libraries to find completely new catalytic solutions. It will be the characterisation and comparison of these diverse systems that may give us unified, quantitative insights into how biocatalysts make the chemistry of life selective and efficient.

Lab members
Ann Babtie, Joanne Cook, Fabienne Courtois, Sean Devenish, Letizia Diamante, Usa Dokphrom, Christopher Hein, Ansgar Hubner, Hans Hufnagel, Stefanie Jonas, Balint Kintses, Celine Lainé, Marcelo Lima, Bert Van Loo, Charlotte Miton, Hiroyuki Ohashi, Luis Olguin, Yolanda Schaerli, Thomas Shafee, Jung-uk Shim, Anastasia Vorobieva, M Yang

References