Enzyme Structure and Mechanism

When Dixon and Webb wrote their classic book 'Enzymes' and the present reviewer wrote 'An Introduction to the Study of Enzymes' to draw attention to new techniques for the study of enzymes, there was no detailed information available about the three-dimensional structure of any catalytically active protein.Ten years ago Bernhard published 'Enzymes Structure and Function' with information about the conformation of the polypeptide chain of lysozyme, ribonuclease and chymotrypsin.Since that time many books have been published on different aspects of enzymology.Some of these were specialised on topics of the authors' expertise and made valuable contributions.Others appear to have been written by non-professionals trying to learn the subject.Such books tend to lack the balance and good advice, which can only come from wide practical experience in the field.Alan Fersht's book has the stamp of an enthusiastic expert.He starts off with two great advantages.First, wide experience in many different aspects of the study of enzyme mechanisms and, secondly, an environment in which he could have many discussions and much advice on the ever increasing number of three-dimensional structures available.The first sentence of the preface highlights his interests and the aspects which are surveyed in detail: 'During the past two decades the advances in X-ray crystallography, transient kinetics and the study of chemical catalysis have revolutionized our ideas on enzyme catalysis and mechanisms'.While the present reviewer does not need convincing that transient kinetics as well as structure studies, and only the two disciplines combined, are needed to elucidate enzyme mechanisms, the general reader will benefit greatly from the synthesis presented in this book.About ten enzymes are treated in some detail, with the experimental approach and the interpretation of data emphasized rather than the theoretical analysis.I have criticised so many books for over-emphasis on steady state kinetics that I find it curious to have to say that this topic is almost too briefly dealt with in the present volume.However, the author does refer to good treatments of steady state kinetics such as that of Cornish-Bowden, just as he refers to the reviewer's 'Enzymes: Physical Principles' for more on transients and other physical topics.Nobody would expect the reviewer and Alan Fersht to agree on all aspects of the historical and technical treatment of enzymology, but it would be churlish to criticise detail in public when one is presented with such an excellent book.One cannot help wondering whether this is the end of an era in enzymology.A lot of detail is known about mechanisms and methods are available to learn a lot more.The study of mechanisms seems to be full of open ended questions.The reviewer feels that the topic will now divide into questions of physical organic chemistry, and specific questions raised by biological problems.This should not discourage further collaboration between the two camps.H.