Lactocepin: the cell envelope-associated endopeptidase of lactococci

The history of the study of proteolytic enzymes (peptidases) can be traced back at least to the late eighteenth century, but in recent times the work has accelerated greatly, fuelled by numerous practical applications in biotechnology, and the realization that these enzymes are major therapeutic targets. Notably, the success of inhibitors of angiotensin converting enzymes for the treatment of hypertension, and retropepsin in the treatment of AIDS has provided an unambiguous validation of the principle that peptidase inhibitors can be successful drugs. The many ways in which proteolytic enzymes impinge on the health and welfare of mankind have made it essential for biological scientists to have ready access to data on peptidases, but the sheer numbers of these enzymes pose a problem. Analysis of complete data on over a hundred genomes has shown that about two percent of all gene products are peptidases, indicating that this is one of the larger functional groups of proteins. The great number of known peptidases creates many practical problems for those needing to work with them. For example, it can be difficult to know how one peptidase can be distinguished from another, how knowledge of one peptidase can help with understanding related peptidases, and how a scientist can recognize a truly novel peptidase. It is such problems that a comprehensive resource such as the present Handbook is designed to help with. The present volume has grown out of a longstanding interest of the editors in preparing readily accessible compilations of data on peptidases. Its genesis can be traced back to the 2nd International Symposium on Intracellular Protein Catabolism organized in Ljubljana, Slovenia, in 1975, by Vito Turk. Two of the original editors (AJB and JFW) recognized that there was the potential for confusion over the various intracellular proteolytic enzymes and how they might be distinguished. A brief document was prepared with the collaboration of I. Kregar and V. Turk, entitled “Present knowledge of proteolytic enzymes and their inhibitors”, and this was published in the proceedings of the conference, Intracellular Protein Catabolism II (V. Turk & N. Marks eds, Plenum Press, New York, 1977). A grand total of 23 intracellular enzymes were tabulated! This modest beginning was followed by Mammalian Proteases: a Glossary and Bibliography by AJB with J. Ken McDonald in two volumes (Academic Press, London, 1980, 1986). Here, 173 peptidases were described in concise summaries supplemented by bibliographies. However, these books have long been out of print. During the 1990s, two of the original editors (AJB, NDR) worked to make use of the wealth of data for the sequences and structures of peptidases that were beginning to appear. They used it as the basis of a new system for the classification of peptidases in which the enzymes were allocated to clans and families within each major mechanistic class. This new classification provided the structure for the MEROPS database when first published on the World Wide Web in 1996. The database formed an easily updatable reference resource containing summary data on all the peptidases. However, it was felt that what was also needed was a supplementary data source which, although not as up-to-date as the website, would provide much a fuller account of the individual peptidases, each having been written by an expert on the enzyme. This resulted in the publication in 1998 of the first edition of the Handbook of Proteolytic Enzymes. The rapid progress of research on proteolytic enzymes continued unabated, and soon after the first publication of the Handbook it was clear that a second edition was needed. Another eight years later, and it was clear that a third edition was required. This present edition contains a great deal of new material; almost all of the chapters have been updated, and there are many new ones. The number of peptidases included now totals well over 1000, and a similar number of authors have worked hard and well to describe these peptidases in the format required for the Handbook. We thank them all for their good work. The present editors wish to take this opportunity to thank the editors of the previous two editions, Alan Barrett (AJB) and Fred Woessner (JFW), who did so much of the original work to establish the style for each chapter. We would also like to thank the team at Elsevier Science, especially Will Smaldon, Janice Audet, and Jacqui Holding for their essential contributions. Finally, we express our heartfelt, personal appreciation to our wives, Cheow-Yong Rawlings and Anna Salvesen, who patiently tolerated our preoccupation with the Handbook during the past several years