Oxford University Press (2000) 347 pages. ISBN 019-8504748

Before reading this book, I would never have believed that a close examination of protein structure could be so animated. Lesk has taken this subject and brought it to life. The book is ideal for readers who have a relatively strong background knowledge of biochemistry but little or no understanding of how protein structure relates to function. In his Preface, Lesk quotes Rutherford, who said, ‘All science is either physics or stamp collecting’. He then explains, ‘This book embodies my reply, that the study of proteins includes the best qualities of both.’ This is an accurate appraisal of the text. The underlying physics of protein architecture is covered in sufficient detail for one to gain an appreciation of proteins as ‘micro-machines’ that function mechanically. At the same time, the book is beautifully illustrated with countless colour figures that impress the variety and elegant complexity of protein structure.

On the first page of the Contents section, there is a note stating ‘Sections marked with an asterisk may be skipped on a first reading’. Then, out of more than 100 sections, only 7 are marked, comprising about 20 of the 300+ pages. Having read this book, I’m sure that the author had a very hard time suggesting that any section could be skipped! His passion for protein architecture emanates from the text, and his enthusiasm will no doubt be infectious for those wishing to learn more about the subject.

Lesk’s literary style makes for easy reading. The text follows a logical organisation in which the reader’s interest is stimulated first by introduction of the photosynthetic reaction centre from Rhodopseudomonas viridis, which ‘illustrates all the essential principles of protein conformation’. He invites, ‘Let us look at it and take it apart.’ Next, there is a description of protein sequence and how 3D structures are derived experimentally. Principles of secondary (helix and sheet) and tertiary structure follow, with extensive reference to classifications of protein structures - for example, in the databases SCOP (http://scop.mrc-lmb.cam.ac.uk/scop) and CATH (http://www.biochem.ucl.ac.uk/bsm/cath/).

Molecular evolution is considered in different contexts and on different time scales. The complicated relationships between amino acid sequence similarity and structural homology with convergent versus divergent evolution are presented in detail. The evolution of function within specific protein families is then highlighted, followed by an introduction to the proteins of the immune system, and the amazingly sophisticated and rapid maturation of the antibody response. Finally, functional aspects of conformational change in proteins are explored.

Throughout the book Lesk keeps his sense of humour, and the reader’s interest, with a few well-placed quips, such as ‘Rotation of the actin during the activity of the [ATPase] was seen and recorded. This movie certainly deserves an Oscar in the natural history category, staring ATPase (and with some fine actin’ in the cast…)’.

Problem sections at the end of each chapter are comprehensive and innovative. In particular, this book is timely in its use of electronic material found on the World Wide Web. A number of the problems (‘weblems’, as they are referred to) require the interactive use of web databases and/or software. However, one drawback of this text is that there are no problem solutions provided.

Understanding how protein function follows form will be one of the great challenges of the 21st century. With the recent boom in sequence data, scientists are now preparing to map out all of protein structure space experimentally. As we seek to navigate the trails of this new universe, Lesk’s book will provide a handy map and a useful guide for many travellers.