Enzymes: what they are and why they are so important

Introduction – Enzymology in 2003

Why the 90th anniversary of v = Vmax x [S] / (Km + [S]) is as important as the 50th anniversary of the double-helical structure of DNA. Enzymology is essential, to find out how nucleic acids fulfil their biological functions. Moreover, genome analysis will always, at some stage in the process, have to advance from sequence gazing to enzymology, since the objective of the analysis must be to identify the reactions mediated by the products of each open reading frame. “Enzymology is thus central to nucleic acid and genomic biochemistry,” says author Stephen Halford.

Contact: Stephen Halford, Department of Biochemistry, University of Bristol, Bristol BS8 1TD; tel: +44 (0)117-928-7429; e-mail: s.halford@bristol.ac.uk

Ancient enzymology?

How did life start to reproduce? In this article David Lilley looks at the mysteries of the RNA world, the time before DNA. “There is a significant chicken-and-egg problem that bedevils imagining how life could have developed on the planet from some kind of primeval soup,” says the author. “All contemporary life uses nucleic acids as the genetic repository and proteins as the chemical workhorse.” Taking the remarkable discovery some 20 years ago that RNA could behave like an enzyme he demonstrates how it could have happened, and explains why the connection between ribozymes and ribosomes is far more than typographical.

Contact: David M. J. Lilley, Cancer Research UK Nucleic Acid Structure Research Group, Department of Biochemistry, MSI/WTB Complex, The University of Dundee, Dundee DD1 5EH; tel.: +44 (0)1382-344243; e-mail: d.m.j.lilley@dundee.ac.uk

Directed evolution

One of the ultimate goals of protein engineers has been to acquire the knowledge to design and build proteins for any given function – for example to produce “tailor-made” enzymes for any given reaction. This has usually been done by modifying an existing protein with a similar function. Although this has resulted in some notable successes, more often it has highlighted our relatively poor understanding of the intricacies of enzyme recognition and catalysis. Here, authors Gavin Williams and Alan Berry describe how they developed an alternative: directed evolution.

Contact: Alan Berry, School of Biochemistry & Molecular Biology, University of Leeds, Leeds LS2 9JT; tel.: +44 (0)113 343 3158; e-mail: A.Berry@leeds.ac.uk

Integral Membrane Enzymes

The design of ’’real’’ integral membrane enzymes must be difficult, because nature uses enzymes of this type only when it really has to. But difficult is not the same as impossible. Anthony Lee looks at the problems and the solutions.

Contact: Anthony Lee, Division of Biochemistry and Molecular Biology, School of Biological Sciences, University of Southampton, Southampton, SO16 7PX; tel.: +44 (0)23 8059 4331; e-mail: agl@soton.ac.uk

Power versus control

More than a third of all enzymes catalyse the oxidation or reduction of a substrate yet the often complex, redox chemistry involved is made possible by surprisingly few cofactors. Stephen Chapman, Simon Daff and Tobias W. B. Ost look at the reasons why.

Contact: Stephen Chapman, School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ; tel.: +44 (0)131 650 4760; e-mail: S.K.Chapman@ed.ac.uk

Single molecule enzymology

We can now measure enzyme activity at the level of a single enzyme molecule. This is technically impressive, but what can it really tell us? Here, Clive R. Bagshaw reviews the basic principles to show that new forms of heterogeneity in activity may be revealed and evidence gained for rare states that would otherwise be swamped in bulk assays.

Contact: Clive Bagshaw, Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7RH; tel.: +44 (0)116 252 3454; e-mail: crb5@le.ac.uk

Product focus: Automated image analysis

Paul Ellwood from Syngene looks at how automated image analysis can improve accuracy and increase productivity in drug discovery.

Contact: Paul Ellwood, Beacon House, Nuffield Road, Cambridge, CB4 1TF; tel: +44 (0) 1223-727123; e-mail: paul.ellwood@syngene.com