The hydrogen exchange behavior of exchangeable protons in proteins can provide important information for understanding the principles of protein structure and function. The positions and exchange rates of the slowly-exchanging amide protons in sperm whale myoglobin have been mapped using 15N-1H NMR spectroscopy. The slowest-exchanging amide protons are those that are hydrogen bonded in the longest helices, including members of the B, E, and H helices. Significant protection factors were observed also in the A, C, and G helices, and for a few residues in the D and F helices. Knowledge of the identity of slowly-exchanging amide protons forms the basis for the extensive quench-flow kinetic folding experiments that have been performed for myoglobin, and gives insights into the tertiary interactions and dynamics in the protein.

By means of a kinetic test, it was demonstrated that one of the folding intermediates (Iα) of hen lysozyme with α-domain folded and β-domain unfolded is on the folding pathway under the classical definition. Iα folds to the native (N) state directly (unfolded (U) [hArr] Iα [hArr] N) without having to unfold to U and then refold to N through alternative folding pathways as in Iα [hArr] U [hArr] N.

Structural genomics projects aim to provide an experimental structure or a good model for every protein in all completed genomes. Most of the experimental work for these projects will be directed toward proteins whose fold cannot be readily recognized by simple sequence comparison with proteins of known structure. Based on the history of proteins classified in the SCOP structure database, we expect that only about a quarter of the early structural genomics targets will have a new fold. Among the remaining ones, about half are likely to be evolutionarily related to proteins of known structure, even though the homology could not be readily detected by sequence analysis.

A search for the occurrence of the rare π-helix was performed with Iditis from the Oxford Molecular Group upon the Protein Data Bank. In 8 of the 10 confirmed crystal structures that harbor the π-helix, its unique conformation has been linked directly to the formation or stabilization of a specific binding site within the protein. In the discussion to follow, the role for each of these eight π-helices will be addressed in regard to protein function. It is clear upon closer examination that the conformation of the π-helix has evolved to provide unique structural features within a variety of proteins.

Alan Fersht has revised his classic text Structure and Mechanism (Freeman, 1985) and extended it to include applications of the protein engineering method to characterizing transition states in protein folding and enzyme catalysis. His earlier textbook was so good it scared off possible competitors, and its notable features are preserved in the new text. It provides enough information about techniques to make close connections between discussions of mechanism and actual data. It packs an amazing amount of information and viewpoint into a short space without losing readability. It does not just derive equations, it explains their physical meanings and it aims to develop the reader's physical insight. The assumptions behind an approach are laid out clearly and, when a topic is controversial, the author gives his own viewpoint at the end. The pace of research today is such that few leading scientists find time to write textbooks, and the scientific community is surely grateful to Alan Fersht for revising his. However, as he points out, a main section of the book covering classical enzymology has not been revised.