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The philosophy of enzymatic catalysis runs earth lives from generation to generation. Slightly structural alteration has allowed various physiological roles of these enzymes that belong to the same class. The substrate specificity distinguishes enzymes from one species to others, forming the base to design drugs specific for human and pesticides specific for pests. This characteristic even benefits the study of organic evolution and novel drugable sites against drug/pesticide resistance. N-acetyl- D-glucosamine and acetylchline related targets, most of which are enzymes, are two examples associated with both drug and pesticides. Various paths, such as biology, toxicology, physiology, chemicobiology and bioinformatics, have been tried. The theme of this issue is to review recent development of these targets in order to reveal how structural changes affect species specificity, efficacy and safety from the point of view of comparative biochemistry.
N-acetyl-D-glucosamine is the building block of oligosaccharide linked to proteins (glycoproteins) or lipids (glycolipids) and chitin as the structural component of insect exoskeleton and cell wall of fungi. N-acetyl-D-glucosaminidases and chitinases are enzymes responsible for hydrolysis of glycosidic bonds joined by N-acetyl-D-glucosamine. The former is important for many life processes including post-translational N-glycan modification, glycoconjugate degradation as well as egg-sperm recognition. And the latter is found to play key roles in insect molting and metamorphism as well as human asthma caused by pathogenic bacteria. For agriculture economy, they are believed to be target potentials in the control of pests and protection of plants. For human, they are specific target potentials in the development of drugs against lysosomal-disorder diseases and pathogenic infection. Thus, the structural comparison of N-acetyl-D-glucosaminidases from different species gives clues to design speciesspecific drugs and pesticides.
Acetylcholine is a neurotransmitter in many organisms including insects and humans. Acetylcholinesterase (AChE) is the most efficient enzyme in existence, which terminates the excitatory effects of neurotransmitter acetylcholine at cholinergic synapses by the hydrolysis of acetylcholine. The interference of the hydrolysis results in a build-up of acetylcholine leading to repeated firing of neurons and ultimately death by exhaustion. The significance of AChE in nerve system makes it an efficient target in developing pesticides. Vertebrate species possess a parallel hydrolase, butyrylcholinesterase (BChE) with detoxification function, which is differentiated from AChE by substrate preferences. This is the base for AchE as a species-specific target in developing insecticides with high selectivity. However given the strong similarities of the insect and mammalian cholinergic nervous system, these AChE-inhibited insecticides are responsible for the million of poisonings and thousands of deaths occurring annually. On the other hand, AChE inhibitors are active against human Alzheimer disease. It is therefore of great importance to reveal structural insights into differences in AChEs from various species.
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