Editorial [Hot Topic: Inhibitors of Serine Proteinases (Guest Editor: M.A. Qasim)]

Interaction of proteinase inhibitors with proteinases is one of the best understood protein-protein interaction systems. The past decade has seen explosive growth in our understanding of the structure and function of proteinase inhibitors and their molecular basis of interaction with proteinases. It is fitting that this issue of Protein and Peptide Letters carries articles on different aspects of inhibitor structure and function by many experts in the field. This issue of Protein and Peptide Letters also represents a pivotal point in the history of standard mechanism serine proteinase inhibitors as it stands between the Michael- Laskowski-Jr. era and the post-Michael-Laskowski-Jr. era. Michael Laskowski Jr. died on August 2, 2004. He was a great pioneer in the field of serine proteinase inhibitors and made numerous remarkable contributions to the field during his fifty-plus years of research. This issue is also a tribute to this great scientist. Nine prominent research groups from all over the world have contributed articles in this issue. The international flavor is quite evident from the fact that there is one article each from Australia, France, Germany, Italy, New Zealand, and Poland, and three articles from different laboratories in the United States. The first article in this issue highlights some of the most important contributions which Michael Laskowski Jr. made to our understanding of serine proteinase inhibitors. The arrangement of other articles is arbitrary, although interested readers would be able to observe some logic in this arrangement. In the second article D. Krowarsch et al. have nicely summarized results obtained on the structure and inhibitory activity of a number of reactive site loop variants of BPTI. The next article by C. Kellenberger and A. Roussel deals with the structure and inhibitory activity of inhibitors belonging to the pacifastin family (the grasshopper family). The fourth article is by T. Komiyama; it describes mutational strategies for the design of inhibitors for furin, Kex2 and PC7 using eglin c as the wild type inhibitor. In the next article H. J. Schirra and D. J. Craik elegantly describe the structure, folding and intramolecular domain swapping in potato II proteinase inhibitors. The sixth article in this issue is by P. Ascenzi et al.; it reviews the mechanism and kinetics of inhibition by small synthetic suicide substrates for thrombin. The seventh article is a review on serine proteinase inhibitors of plant origin by J. Christeller and W. Laing. The next article is by W. Hohne and K. Hilpert and discusses the applications of substitutional analysis by cellulose-bound peptide spot synthesis for the characterization and optimization of several small polypeptide inhibitors. In this issue, which is heavily biased towards inhibitors of serine proteinases, the article by M. Sahin-Toth represents an interesting departure. Inhibitors are not always the winners, and occasionally enzymes use tricks to evade inhibition and sometimes even digest them. This scenario has been nicely reviewed by M. Sahin-Toth with special reference to mesotrypsin. The last article in this issue is by C. Kelly et al. and deals with the role of scaffolding in the structure, stability, and inhibitory activity of standard mechanism serine proteinase inhibitors. Although this issue is devoted to serine proteinase inhibitors and serine proteinases and would be of great interest to researchers in these areas, it should also be of interest to protein chemists involved in structure-function studies and to those who care about protein-protein interactions.