Glycoside hydrolase family 18 chitinases: The known and the unknown

Genomic and transcriptomic landscapes and evolutionary dynamics of molluscan glycoside hydrolase families with implications for algae-feeding biology

“…GH18 family genes are widely distributed in representatives of all kingdoms. Extensive studies on the domain architecture, functional divergence and structure-function relationship have been carried out in mammals, insects, plants, fungi, bacteria, archaea, nematodes and viruses [92] , [93] , [94] . However, little is known about the characteristics and evolution of the molluscan GH18 family.…”

Structural inspection and protein motions modelling of a fungal glycoside hydrolase family 18 chitinase by crystallography depicts a dynamic enzymatic mechanism

“…GH18 chitinases represent an ancient type of enzymes found in all kingdoms of life, sharing a catalytic TIM-barrel domain and showing a substrate-assisted catalytic mechanism where a conserved glutamate residue (included in the DXDXE catalytic motif) protons the glycosidic bond to be hydrolyzed (forming an oxazolinium ion intermediate), and the oxygen of the N-acetyl group of NAG in the subsite −1 sugar acts as nucleophile [7] , [8] . Evidences from kinetic studies, crystal structure analysis and molecular dynamics simulations depicted crucial features as the role of the catalytic aspartates, the stabilization of the oxazolinium intermediate by the enzyme, or the distortion of the stereochemistry of substrates leading to glycosidic bond cleavage (for an updated review see [9] and references therein).…”

Structure-based virtual screening of highly potent inhibitors of the nematode chitinase CeCht1

“…GH18 chitinases hydrolyse b-1,4-glycosidic bonds in chitin and chitooligosaccharides. As chitin is present in the eggshell, cuticle, pharynx and microfilarial sheath of nematodes [1][2][3][4][5] , nematode chitinases have been shown to play an important role in various physiological processes, including egg hatching, larva moulting, and reproduction [6][7][8] . Downregulating the expression level of nematode chitinases led to hatching delay and moulting defects in many nematode species, such as the free-living model nematode Caenorhabditis elegans, the plant parasitic nematode Bursaphelenchus xylophilus, and the animal parasitic nematodes Acanthocheilonema viteae and Onchocerca volvulus [9][10][11] .…”

“…The importance of nematode chitinases indicates that they may be promising nematicide targets for the development of small-molecule inhibitors for nematode pest control 12 . Many GH18 chitinase inhibitors with diverse scaffolds have been reported so far, and some showed potential applications as antifungal agents, pesticides, and drugs 6,[13][14][15] . However, the inhibition of nematode chitinases is rarely studied, and only few inhibitors have been reported to be effective on nematode chitinases, including allosamidin, closantel, b-carboline, and 4-hydroxy-1,2,3-triazoles.…”