Introduction to proteins—structure, function, and motion

Q 2012 by The International Union of Biochemistry and Molecular Biology

BIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION Vol. 40, No. 3, pp. 218, 2012

Book Review Introduction to Proteins—Structure, Function, and Motion Amit Kessel and Nir Ben-Tal, CRC Press, Boca Raton, FL, USA, 2011, 626 pp., ISBN 978-1-4398-1071-2 (hardcover, $79.95). Also available as e-book. Introduction to Proteins by Kessel and Ben-Tal is an excellent, state-of-the-art choice for students, faculty, or researchers needing a monograph on protein structure. It is unusual, among monographs dealing primarily with structure versus function, in including protein dynamics and energetics in considerable detail. It is also unusual in its strong, detailed coverage of membrane proteins (81 pages, Chapter 7), 20 pages on post-translational modifications, and 14 pages on intrinsically unstructured proteins. G-protein coupled receptors are given thorough coverage (23 pages). The book is clear, well organized, aptly illustrated in color, and a pleasure to read. The first two chapters are an impressive textbook unto themselves: 190 pages introducing ‘‘the importance of proteins in living organisms,’’ including a useful review of the biochemistry of living systems, diversity of proteins and their functions. The book continues by reviewing noncovalent bonds, pKa, primary, secondary, tertiary and quaternary structure, and post-translational modifications. Particularly excellent are the introductions to amyloidoses and protein misfolding, chaperonins, allostery, and hemoglobin. Globular proteins are covered amply throughout the book, and there are 25 pages on fibrous proteins emphasizing function-structure relationships, with examples primarily from eukaryotic cells. The final chapter deals with proteinligand (including protein-protein) interactions, including a clear discussion of lock-and-key, induced fit, and population shift models, as well as free energies of binding. Chapter 3 offers a 43 page overview of ‘‘methods of structure determination and prediction.’’ Although useful as far as it goes, this is one of the weaker chapters. It does not emphasize that the protein must be soluble for all common methods of structure determination, does not mention the use of heavy metals or selenomethionine for phase determination, and fails to offer much guidance on evaluation of the quality of crystallographic or NMR models. Free R and temperature factor (B factor) are not mentioned. Thought-provoking opinions are occasionally stated. For example, after introducing SCOP and CATH: ‘‘The problem of finding a single foolproof classification method may result . . . from the protein structural space being continuous . . .. even apparently different structures may share common features such as secondary structure arrangement. If this is indeed true, classifying proteins into discrete structural categories may be pointless.’’ (p. 157–8) The book is thoroughly documented with citations to the literature gathered at the end of each chapter. All references include titles. For example, Chapter 7 on membrane proteins cites 400 references, including many DOI 10.1002/bmb.20603

as recent as 2009. The entire book cites nearly 2,000 references. PDB identification codes are frequently given for the examples described, making it easy to visualize them in 3D. Unfortunately, no guidance is given regarding visualization software. The book’s website offers only a set of study questions, about a dozen for each of the eight chapters. These are generally thought-provoking and useful, and answers, as well as slides, are said to be available to instructors on request from the publisher (p. xxiii). There are a few topics that deserved greater coverage. Not conveyed are the prevalence of cation-pi interactions, and their importance in the energetics of protein folding and in ligand-protein interactions (e.g., acetylcholinesterase, nicotine addiction). The absence of cation-pi interactions in the introduction to noncovalent interactions is conspicuous. An otherwise extensive discussion of hemoglobin structure versus function omits mention of malaria as an evolutionary pressure maintaining sickle hemoglobin. Although protein engineering is introduced briefly, some coverage of recent successes with enzyme re-targeting would be useful. There are rare errors, such as describing lipids as macromolecules, and lumping the effect of mercaptoethanol in Anfinson’s denaturation of RNAse under ‘‘disrupting noncovalent forces’’ (p. 103). The English is excellent, with very rare minor slips, such as calling the ends of protein chains their ‘‘edges’’ or the thickness of a lipid bilayer its ‘‘width.’’ Although extremophiles are introduced briefly (p. 288), I did not see mention of the frequent successes crystallographers have had with proteins from thermophiles. Although mechanisms of thermostabilization are discussed, I saw no mention of the role of salt bridges. The terms thermophile, thermostability, and hyperthermophile did not make it into the index, although the index is 34 pages long and generally quite useful. Many of the many acronyms used throughout the book made it into the index, but some did not (e.g., PFAM, CL). The book concludes with an extensive treatment of ligand-protein interactions, including 30 pages on drug action and design. A clear 20-page overview and explanation of various techniques is followed by a 10-page case study of the rational design of angiotensin conversion enzyme inhibitors. Overall, this is an immensely informative, thoroughly researched, up to date text, with broad coverage and remarkable depth. Introduction to Proteins would provide an excellent basis for an upper level or graduate course on protein structure, and a valuable addition to the libraries of professionals interested in this centrally important field.

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Eric Martz Department of Microbiology University of Massachusetts Amherst, Massachusetts 01003 This paper is available on line at http://www.bambed.org