Editorial [Hot Topic: Hydrolase Versus Other Functions of Members of the Alpha/Beta-Hydrolase Fold Superfamily of Proteins (Guest Editor: Pascale Marchot and Arnaud Chatonnet)]
This Special Issue gathers eight timely review articles about the structure, function, and evolutionary relationships of the members of the alpha/beta-hydrolase fold superfamily of proteins. Most of the proteins in this superfamily display hydrolytic functions carried by a canonical
triad of catalytic residues, which serve to catalyze the hydrolytic cleavage of a range of properly oriented substrates with various chemical characteristics. Yet a small set of the family members are devoid all or some of these catalytic residues, and several of these “non-hydrolase”
proteins have been characterized at the structural and functional levels. However, these studies raised many questions, such as: To what extent can a protein perform two functions? Should the two functions be distinctive? Could they involve a single binding/recognition site or should the sites
be distinctive? Can the two functions be performed simultaneously, or is each of them related to a specific cell or time environment dictating its turning on/off? Could a protein molecule switch from the one to the other function during evolution?
The ESTHER database was designed 15 years
ago to collect, annotate, organize and diffuse information related to the alpha/beta-hydrolase superfamily. The web server allows one to retrieve figures highlighting the need for more experimental data on structure and function of numerous proteins that are only related by sequence [1,2].
Indeed, among the thousands of proteins that share only limited sequence homology in the database, only 270 proteins belonging to 54 subfamilies have been crystallized, although this number increases steadily each year (figure 1). As well, in the human genome 121 genes have been shown to encode
alpha/beta-hydrolase fold proteins, of which 20 apparently lack a functional catalytic site. A functional role has been described for only a few of the later, of which at least three (rbbp9, egasyn CIB) both display an enzymatic activity and participate in protein assemblies. Of the 31 human
alpha/beta-hydrolases that have been crystallized, three (neuroligin, ndr2, dpp6) are not enzymes. Twenty-two members of the superfamily were shown to be responsible for genetic diseases when mutated, and modification of expression of many other members are suspected to be responsible for
clinical symptoms in specific diseases. For a few of these, an anti-oncogene role has been reported (e.g., OVCA2). The characterization of other nonenzyme alpha/beta-hydrolases in insects, plants or bacteria can also shed light on evolution of this widely represented superfamily.
Special Issue encompasses eight chapters, corresponding to five reviews and three original articles. The opening chapter, a review by the guest editors P. Marchot and A. Chatonnet (France), provides readers with a panorama of the bestknown examples of protein-protein interactions in the most
prominent families composing the superfamily, and presents some of the current knowledge about common or divergent modes of protein interactions . In the second chapter, G. Manco and colleagues (Italy and China) review the various types of “promiscuity” encountered in the superfamily
and provide examples of natural or directed evolution of enzymes in the hormone-sensitive lipase like subfamily . In the third and fourth chapters, A. Vogel-Hopker and colleagues (Germany) and A. Halliday and S. Greenfield (Great Britain) review several of the pleiotropic functions of acetylcholinesterase,
otherwise known as the enzyme that hydrolyzes the neurotransmitter acetylcholine to regulate functioning of cholinergic synapses, and a prototype in the COesterase family (Pfam PF00135) [6,7]. The fifth chapter, by A. De Jaco and colleagues (Italy and USA), reviews the natural mutations affecting
the alpha/beta-hydrolase domain in an enzyme, in a synaptic cell adhesion protein and prototype of non-catalytic hydrolase in the family, and in a hormone receptor, and shows how these mutations impair processing and trafficking of the altered proteins along the secretory pathway . In the
sixth chapter, an original article by K. Hirano and colleagues (Japan) presents a comprehensive structural and functional analysis of the nuclear receptor to the gibberellin phytohormones, a non-hydrolase member of the hormone-sensitive lipase subfamily . In the seventh chapter, an original
article by C. Bahl and D. Madden (USA) reports the structure of an inactive mutant of Cif, a member of the epoxide hydrolase subfamily and virulence factor that reduces the functional localization of the CFTR channel in epithelial cells . And the eighth chapter, an original article by
S. Vorobiev and colleagues (USA), addresses the uncommon theme of assessing a hydrolytic function for a protein initially known for partnership interactions only . Hence, we feel that this Special Issue, although not fully comprehensive, highlights the widely diverse aspects of promiscuity
and moonlighting activities  performed by members of the alpha/beta-hydrolase fold superfamily of proteins.
We thank all and each of the authors for their enthusiastic and efficient contribution to this Special Issue and patience towards the timetable and delays. We hope they approve
the order in which the chapters are organized (a difficult choice) and are proud to share this literature contribution with us. At least two referees, selected among the authors or other colleagues, carefully reviewed each manuscript. We thank all the referees for the serious, constructive
and efficient work.....
Document Type: Research Article
Publication date: February 1, 2012
More about this publication?
Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.