Posttranslational modification of proteins: Expanding nature's inventory. Christopher T. Walsh, Roberts & Company Publishers, Greenwood Village, CO, 2005, 576 pp., ISBN 0-9747077-3-2, $98.00
Educators in biochemistry, molecular biology, and other related life sciences are continually searching for resources to help them incorporate rapidly developing topics into their classes. One such hot, cutting-edge topic today is the posttranslational modification (PTM)1 of proteins, the myriad of reactions that chemically alter protein side chains and main-chain peptide bond connectivity after the protein emerges from synthesis on the ribosomes (translation). Most of us have been informing our students of the well known PTM examples of proteolytic cleavage, modification of amino acids (phosphorylation, acetylation, etc.), and attachment of carbohydrates. However, in recent years, the repertoire of known PTM reactions has expanded dramatically. The author, who is an active researcher in this area, wrote Posttranslational Modification of Proteins: Expanding Nature's Inventory because he was unable to find any contemporary or comprehensive survey of the field in the literature. With this text, Professor Walsh not only helped himself, but he has also provided a valuable resource for all of us by finally bringing some order and clarity into the dizzying array of PTMs.
The book is comprised of 16 chapters, beginning in the first chapter with a brief review of protein biosynthesis (translation), a general survey of the scope of PTM reactions, and a discussion of the techniques and procedures applied to the study of protein modification processes. Chapters 2–15 describe the varieties of PTM processes and are organized according to the type of chemical reaction and necessary enzymes. The order of topics is: phosphorylation, sulfation, Cys/Met oxidation, methylation, N-acetylation, lipidation, proteolysis, ubiquitylation, glycosylation, ADP-ribosylation, hydroxylation, automodification, carboxylation, and modification with swinging arms (biotin, lipoate, and phosphopantetheine). The final chapter covers the PTM diversity present in the proteome. The chapters range in size from about 20 to 50 pages.
Biochemical reactions and processes outlining PTM reactions are explained using rigorous chemical mechanisms, but this is what we would expect from the author of the classic text, Enzymatic Reaction Mechanisms, a textbook we have all used and loved. Especially helpful are the references listed at the end of each chapter. Instead of an inclusive listing of all historical and current citations, Professor Walsh has chosen to select only recent review articles to provide an entry to the various reactions. Most references, which number from about 20 to 50 per chapter, are from the 21st century.
The text is appropriate for several pedagogical uses. It may be used in a general one-year biochemistry or cell biology class as a supplement to one of the standard texts. Students with a full year of strong organic chemistry should have no difficulty understanding the mechanistic discussions that are described with excellent clarity. Because the chapters are written so that they stand alone, students could achieve understanding from selected chapters without reading the entire text. It could also be used for a one-semester special topics course for advanced undergraduate students and graduate students in biochemistry, molecular biology, and related life sciences. Even if you are an expert and carry out research on PTMs, you will discover new and interesting information in this book.
Biologists will be pleased to find discussions on the biological roles of protein modification. Examples include PTM processes that have influence on signal cascades, neurochemical signaling, protein conformational changes, modulation of enzyme action, changes in cellular location of proteins, and of course, regulation of metabolism.
The text is enhanced with the incorporation of excellent illustrations and tables that are present on almost every page. Although they are mainly in black and white (with occasional red highlighting), they are clear and complete. The reviewer quibbles with only one figure; it would be more appropriate to show the amino acids in zwitterionic form rather than in unionized form in Fig. 1.2. The author was especially adept at weaving into the discussion examples of how the development of new procedures in mass spectroscopy, x-ray crystallography, capillary electrophoresis, two-dimensional electrophoresis, and HPLC has been essential in solving complex problems in the study of PTMs.
Professor Walsh assures us that we have not seen the end of important discoveries in this area. He predicts that we will continue to uncover new and intriguing PTM processes that will help us explain and understand the molecular intricacies of simple and complex organisms.