About this Research Topic
Metal containing enzymes or metalloenzymes are ubiquitous in nature, being widespread in both animal and plant kingdom including the microorganisms, constituting about a third of all known enzymes. In metalloenzymes, the metal ion can be a co-factor, hence necessary and directly involved in the enzymatic catalytic reaction. Alternatively, the metal ion can be a part of a prosthetic (non-protein) group of the metalloenzyme such as the heme group present in hemo/myoglobin and cytochromes. These metal ions are essential for either catalytic activity or structural stability of the metalloenzyme.
Many proteins contain metal binding domains; the most familiar example is of zinc fingers, a Zn (although other metal ions can also be present) bound structural motif found in a variety of metalloproteins, often called zinc finger proteins. These zinc fingers are essential for protein-protein or protein-nucleic acid, specific recognition and binding.
Metalloenzymes play a key role in regulating various metabolic pathways and physiological functions. Irregularities (often overexpression) in the activity of these metalloenzymes is responsible for a variety of disorders and diseases, hence the therapeutic role of metalloenzyme inhibitors is well established and well-exploited, and is an area of active research worldwide. Inhibitors of metalloenzymes are usually small molecules that act as metal binding groups (MBGs), coordinating with metal ions present in the active site of the metalloenzymes. A broad range of structural moieties have been known to act as metal binding groups (MBGs), such as carboxylate, hydroxamic acid, thiol, N-hydroxyurea, and sulfonamide groups. Metalloenzymes are important drug targets, such as carbonic anhydrases, ectonucleotidases (alkaline phosphatase (AP), ecto-5’-nucleotidase (e5NT), nucleoside triphosphate diphosphohydrolase (NTPDase) and nucleotide pyrophosphatase/phosphodiesterase (NPP)), urease, matrix metalloproteinases (MMPs), tyrosinase, HIV-1 integrase, histone deacetylase (HDAC-2) and angiotensin converting enzymes (ACE).
This Research Topic will focus on metalloenzymes as novel drug targets, their physiological significance and therapeutic applications of their inhibitors and activators.
Keywords: Metalloenzyme inhibitors, nucleotide metabolizing enzymes, tyrosinase, urease, carbonic anhydrases
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