oa Editorial [Hot Topic: Plant Protease Inhibitors, a Panoply of Enzymes for Plant Defense, and Not Only (Guest Editor: Luigi R. Ceci)]

Plant protease inhibitors (PIs) continue to exert interest among plant biochemists and biotechnologists in spite of the (almost complete) failure in the production of transgenic crops with enhanced resistance toward insects. Indeed, plant PIs still offer an ample space for both applicative and basic researches. The huge reservoir provided by the Plant Kingdom, the development of investigative methodologies and biotechnologies and the possibility to apply plant PIs in different fields than crop protection, are at the basis of this ongoing interest. This special issue is aimed at providing readers with an update on the characterization of the numerous families of plant PIs, together with an overview of their possible applications. In addition it gives an interesting example of a co-evolutive adaptation, which allows plants and insects to co-exist for millions of years with mutual benefit. The first four articles introduce plant PIs. Katherine Bateman and Michael James [1] provide a detailed discussion about structural analysis of plant PIs and, when known, of their complexes with proteases. Authors give examples of the threedimensional structures available for almost all the families of PIs, allowing readers to better understand the basic mechanisms of inhibition. The review article by Maria Luiza Oliva et al. [2] reports about the structural and functional properties of one of the largest and most largely known family of plant PIs, the Kunitz family, in Leguminosae plants. Examples of studies on the pharmacological action of Kunitz inhibitors are also given. Alfonso Clemente et al. [3] besides reporting about the structure, inhibitory mechanism, diffusion and nutritional properties of the Bowman-Birk inhibitors in legumes, give a wide and critical review of the potential use of members of this PI family as anti-carginogenic and anti-inflammatory agents. David Turra and Mateo Lorito [4] deal with two PIs families, firstly detected in potato: potato type I (Pin1) and II (Pin2). Together with the structure, activity and protective role of enzymes belonging to these families, authors also outline their physiological role in plants and potential application in medicine. The other main families of plant PIs are described in the review by Volpicella et al. [5] allowing readers to appreciate the variety of inhibitors of which plants provided themselves. In addition the article illustrates examples of inhibitors of the cystatins and mustard inhibitor families, which have been largely modified by directed evolution techniques. A review is dedicated to illustrate the discovery, characteristics and functional role in the induction of plant PIs of systemin, the first plant peptide hormone. The pioneering work on this topic reported by Greg Pearce [6] revolutionized the field of peptide signaling in plants. In the subsequent years, additional systemin-like peptides and other signaling peptides were identified in plants, thus establishing the essential role of signaling peptides in many plant processes. The article by John Gatehouse [7] reports a critical evaluation of the reasons why engineering PIs genes in plants have reached a limited application for increasing resistance of crops toward insects. In addition it analyses the possibility that PIs, used in combination with other insecticidal proteins or thanks to their possible action on different physiological processes than digestion, could have chances to be further employed for plant protection. Two articles follow that focus on natural targets of plant PIs. In the article by Marco Gomes et al. [8] a detailed report about the four main families of plant proteases, together with their biochemical features, physiological role and the potential pharmacological activity is given. Marteen Jongsma and Jules Beeckwilder [9] highlight in their review the adaptive capacity of insects to plant PIs, achieved by the expression of proteases insensitive to inhibition. Authors focus on the structural effects that relatively few modifications in the primary structure of proteases can produce, resulting in lower affinities toward PIs. This successful (by the insect point of view) mechanism is regarded as an aspect of the co-evolution of insect proteases and plant PIs. The last article by Arianna Consiglio et al. [10] is dedicated to the description of a web resource for the retrieval of information available on more than 1,000 plant PIs. The PlantPIs database offers the possibility to obtain information on single PIs in an organized way, useful to either expert scientists or students. Together, the articles in this special issue provide an exciting overview of current research on plant PIs that hopefully will stimulate readers to devise the next generation of experiments in this area.....