oa Editorial [ Hot Topic-II: Zinc Metallo-Enzymes as Target for Drug Design (Guest Editor: Giuseppina De Simone )]

Starting from the discovery in 1940 of the first zinc metalloenzyme, carbonic anhydrase II, a very large number of enzymes requiring zinc as essential cofactor has been identified in all organisms, showing a variety of important physiological functions. These enzymes have a wide range of specific biological activities residing in the intra- and extracellular environments, and are implicated in several types of pathologies, such as cancer, cardiovascular and neuronal degenerative diseases, atherosclerosis, glaucoma and inflammation. For this reason, they are very attractive targets for drug design, and some of their inhibitors are commonly used for pharmacological treatment during pathology. Even though several drugs have been so far designed and developed against zinc metalloenzyme targets, there is still need of progress and improvement in this research area. The importance and wide variety of zinc-containing enzymes induced me to focus this issue on some members of this family that have been shown to be relevant for biomedical applications. In particular, carbonic anhydrases (CAs), metalloproteases (MPs), angiotensin-1 converting enzyme (ACE) and glutamate carboxypeptidase II (GPII) have been chosen as representative examples. CAs are ubiquitous metallo-enzymes present in prokaryotes and eukaryotes and encoded by five evolutionarily unrelated gene families: α,β,γ,δ,ζ and . Since their discovery, these enzymes have been widely investigated due to their important pathophysiological roles in all kingdoms of life. The first paper of this special issue is focused on carbonic anhydrase IX (CA IX), a human member of this family, which has recently been shown to be a marker of tumor hypoxia and a prognostic factor in several human cancers. The most recent catalytic and structural features uncovered of this enzyme have been comprehensively summarized by the Authors, highlighting how this information has been exploited to develop antibodies and small molecules with therapeutic potential. CAs, this time isolated from bacterial sources, as well as zinc MPs are the topic of the second paper, which overviews in vitro and in vivo biochemical and inhibition studies reported for these enzymes so far. It is highlighted the importance of this research since in some cases bacterial proteins can represent future drug targets for obtaining conceptually novel antibiotics.