This review describes the life of Sir John Cornforth AC CBE FRS, who was awarded the Nobel Prize for Chemistry in 1975. It covers his early life in Australia, his work in Oxford, the National Institute for Medical Research, the Milstead Laboratory of Chemical Enzymology and the University of Sussex, together with the contributions made by his wife, Lady Rita Cornforth.

The abnormal shape and poor deformability of the sickled erythrocyte (RBC) have generally been held responsible for the microvascular occlusions of sickle cell disease. However, there is no correlation between the clinical severity of this disease and the presence of sickled RBC. In searching for additional factors that might contribute to the pathophysiology of sickle cell disease, we have inv...

The early time course of adaptation of pulmonary O(2) uptake (Vo(2)(p)) (reflecting muscle O(2) consumption) and muscle deoxygenation kinetics (reflecting the rate of O(2) extraction) were examined during high-intensity interval (HIT) and lower-intensity continuous endurance (END) training. Twelve male volunteers underwent eight sessions of either HIT (8-12 x 1-min intervals at 120% maximal O(2...

DNA glycosylases safeguard the genome by locating and excising a diverse array of aberrant nucleobases created from oxidation, alkylation, and deamination of DNA. Since the discovery 28years ago that these enzymes employ a base flipping mechanism to trap their substrates, six different protein architectures have been identified to perform the same basic task. Work over the past several years ha...

In enzymology, as in organic chemistry, many transformations revolve around the chemistry of the carbonyl group. A carbonyl group is electrophilic how can it be made more so? Hydrogens next to a carbonyl group have a reduced pK, how can this reactivity be promoted? Nature has found several ways to address these mechanistic challenges, the most important of which is the use of imines. Studies on...

One of the most controversial questions in enzymology today is whether protein dynamics are significant in enzyme catalysis. A particular issue in these debates is the unusual temperature-dependence of some kinetic isotope effects for enzyme-catalysed reactions. In the present paper, we review our recent model [Glowacki, Harvey and Mulholland (2012) Nat. Chem. 4, 169-176] that is capable of rep...

Simulations and modelling [e.g. with combined QM/MM (quantum mechanics/molecular mechanics) methods] are increasingly important in investigations of enzyme-catalysed reaction mechanisms. Calculations offer the potential of uniquely detailed, atomic-level insight into the fundamental processes of biological catalysis. Highly accurate methods promise quantitative comparison with experiments, and ...

BACKGROUND Chemistry and particularly enzymology at surfaces is a topic of rapidly growing interest, both in terms of its role in biological systems and its application in biocatalysis. Existing protein immobilization approaches, including noncovalent or covalent attachments to solid supports, have difficulties in controlling protein orientation, reducing nonspecific absorption and preventing p...

This study offers a detailed mechanistic investigation of host-guest encapsulation behavior in a new enzyme-mimetic metal-ligand host and provides the first observation of a conformational selection mechanism (as opposed to induced fit) in a supramolecular system. The Ga4L4 host described features a C3-symmetric ligand motif with meta-substituted phenyl spacers, which enables the host to initia...

Mechanistic models for biochemical systems are frequently proposed from structural data. Site-directed mutagenesis can be used to test the importance of proposed functional sites, but these data do not necessarily indicate how these sites contribute to function. In this study, we applied an alternative approach to the catalytic mechanism of alkaline phosphatase (AP), a widely studied prototypic...