{PDOC00839} {PS01095; GH18_1} {PS51910; GH18_2} {BEGIN} ********************************************************************************* * Glycosyl hydrolases family 18 (GH18) active site signature and domain profile * ********************************************************************************* The glycosyl hydrolases family 18 (GH18) [E1] is widely distributed in all kingdoms, including viruses, bacteria, plants, fungi and animals. The GH18 family contains hydrolytic enzymes with chitinase or endo-N-acetyl-beta-D- glucosaminidase (ENGase) activity as well as chitinase like lectins (chi- lectins/proteins (CLPs). Chitinases (EC 3.2.1.14) are hydrolytic enzymes that cleave the beta-1,4-bond releasing oligomeric, dimeric (chitobiose) or monomeric (N-actetylglucosamine, GlcNAc) products. ENGases (EC 3.2.1.96) hydrolyze the beta-1,4 linkage in the chitobiose core of N-linked glycans from glycoproteins leaving one GlcNAc residue on the substrate. CLPs do not display chitinase activity but some of them have been reported to have specific functions and carbohydrate binding property. The catalytic domain of GH18s may be connected to one or several substrate binding modules (CBMs), which enhance binding of enzymes to insoluble substrates. Certain GH18s also contain peptide signals for localization such as an N-terminal secretion peptide, a C- terminal glycosyl-phosphatidylinositol (GPI) anchor signal for attachment to the plasma-membrane, or N- or O-linked glycosylation sites for oligosaccharide modifications [1,2,3,4,5,6,7,8,9]. The catalytic domain of GH18s has a common (beta/alpha)8 triosephosphate isomerase (TIM)-barrel structure, which consists of a barrel-like framework made from eight internal parallel beta-strands that are alternately connected by eight exterior alpha helices (see ). The active site motif DxxDxDxE is essential for the activity of the GH18 catalytic domain. The Glu (E) in this motif acts as the catalytic proton donor, and the last Asp (D(3)) is supposed to contribute to the stabilization of the essential distortion of the substrate [3,4,5,6,7] We used a region centered around the active site motif as a signature pattern and we have also developed a profile that covers the entire GH18 catalytic domain. -Consensus pattern: [LIVMFY]-[DN]-G-[LIVMF]-[DN]-[LIVMF]-[DN]-x-E [E is the active site residue] -Sequences known to belong to this class detected by the pattern: ALL, except for conB which has a Gln instead of the active site Glu. -Other sequence(s) detected in Swiss-Prot: 1. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Expert(s) to contact by email: Neuhaus J.-M.; jean-marc.neuhaus@bota.unine.ch Henrissat B.; bernie@afmb.cnrs-mrs.fr -Last update: October 2019 / Text revised; profile added. [ 1] Badariotti F., Lelong C., Dubos M.-P., Favrel P. "Identification of three singular glycosyl hydrolase family 18 members from the oyster Crassostrea gigas: Structural characterization, phylogenetic analysis and gene expression." Comp. Biochem. Physiol. 158B:56-63(2011). PubMed=20868765; DOI=10.1016/j.cbpb.2010.09.009 [ 2] Tzelepis G.D., Melin P., Jensen D.F., Stenlid J., Karlsson M. "Functional analysis of glycoside hydrolase family 18 and 20 genes in Neurospora crassa." Fungal. Genet. Biol. 49:717-730(2012). PubMed=22796096; DOI=10.1016/j.fgb.2012.06.013 [ 3] Terwisscha van Scheltinga A.C., Hennig M., Dijkstra B.W. "The 1.8 A resolution structure of hevamine, a plant chitinase/lysozyme, and analysis of the conserved sequence and structure motifs of glycosyl hydrolase family 18." J. Mol. Biol. 262:243-257(1996). PubMed=8831791; DOI=10.1006/jmbi.1996.0510 [ 4] Tsuji H., Nishimura S., Inui T., Kado Y., Ishikawa K., Nakamura T., Uegaki K. "Kinetic and crystallographic analyses of the catalytic domain of chitinase from Pyrococcus furiosus- the role of conserved residues in the active site." FEBS. J. 277:2683-2695(2010). PubMed=20553502; DOI=10.1111/j.1742-464X.2010.07685.x [ 5] Schimpl M., Rush C.L., Betou M., Eggleston I.M., Recklies A.D., van Aalten D.M.F. "Human YKL-39 is a pseudo-chitinase with retained chitooligosaccharide-binding properties." Biochem. J. 446:149-157(2012). PubMed=22742450; DOI=10.1042/BJ20120377 [ 6] Stals I., Karkehabadi S., Kim S., Ward M., Van Landschoot A., Devreese B., Sandgren M. "High resolution crystal structure of the endo-N-Acetyl-beta-D-glucosaminidase responsible for the deglycosylation of Hypocrea jecorina cellulases." PLoS One. 7:E40854-E40854(2012). PubMed=22859955; DOI=10.1371/journal.pone.0040854 [ 7] Madhuprakash J., Singh A., Kumar S., Sinha M., Kaur P., Sharma S., Podile A.R., Singh T.P. "Structure of chitinase D from Serratia proteamaculans reveals the structural basis of its dual action of hydrolysis and transglycosylation." Int. J. Biochem. Mol. Biol. 4:166-178(2013). PubMed=24380021 [ 8] Patil D.N., Datta M., Dev A., Dhindwal S., Singh N., Dasauni P., Kundu S., Sharma A.K., Tomar S., Kumar P. "Structural investigation of a novel N-acetyl glucosamine binding chi-lectin which reveals evolutionary relationship with class III chitinases." PLoS One. 8:E63779-E63779(2013). PubMed=23717482; DOI=10.1371/journal.pone.0063779 [ 9] Junges A., Boldo J.T., Souza B.K., Guedes R.L.M., Sbaraini N., Kmetzsch L., Thompson C.E., Staats C.C., de Almeida L.G.P., de Vasconcelos A.T.R., Vainstein M.H., Schrank A. "Genomic analyses and transcriptional profiles of the glycoside hydrolase family 18 genes of the entomopathogenic fungus Metarhizium anisopliae." PLoS One. 9:E107864-E107864(2014). PubMed=25232743; DOI=10.1371/journal.pone.0107864 [E1] http://www.cazy.org/GH18.html -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}