Recent structural insights into the expanding world of carbohydrate-active enzymes Gideon J Davies , Tracey M Gloster and Bernard Henrissat

Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW, UK.
Current Opinion in Structural Biology (Impact Factor: 7.2). 01/2006; 15(6):637-45. DOI: 10.1016/
Source: PubMed


Enzymes that catalyse the synthesis and breakdown of glycosidic bonds account for 1-3% of the proteins encoded by the genomes of most organisms. At the current rate, over 12 000 glycosyltransferase and glycoside hydrolase open reading frames will appear during 2006. Recent advances in the study of the structure and mechanism of these carbohydrate-active enzymes reveal that glycoside hydrolases continue to display a wide variety of scaffolds, whereas nucleotide-sugar-dependent glycosyltransferases tend to be grafted onto just two protein folds. The past two years have seen significant advances, including the discovery of a novel NAD+-dependent glycosidase mechanism, the dissection of the reaction coordinate of sialidases and a better understanding of the expanding roles of auxiliary carbohydrate-binding domains.

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Available from: Tracey M Gloster, Sep 30, 2015
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    • " in the 35S : : ANAC012 plants . Fifteen genes ( 7 . 4% ) classified in the ' biogenesis of cell wall ' category were upregulated by transient overexpression of ANAC012 ( Table S4 ) . Seven of theses encode glycoside hydrolase , which hydrolyze glycosidic bonds between car - bohydrates or between a carbohydrate and a non - carbohy - drate moiety ( Davies et al . , 2005 ) . Three of them encode pectinesterase . Both glycoside hydrolase and pectinesterase are involved in cell - wall modification and re - structuring ( Aspeborg et al . , 2005 ; Bosch et al . , 2005 ; Jiang et al . , 2005 ) . This result is consistent with the notion that ANAC012 acts as a negative regulator for xylary fiber formation . W"
    • "Since then, the exploding number of 3D structures during the 1990s revealed that a plethora of folds may catalyse the same reaction. For example, the first cellulase structures revealed 6 or 7 different topologies (Davies and Henrissat, 1995; Vasella et al., 2002; Davies et al., 2005; Fushinobu et al., 2013). Indeed, the existence of such a broad range of folds catalysing the same reaction demonstrates the immense versatility of protein scaffolds. "
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    ABSTRACT: Glycosidases catalyse the hydrolysis of glycosidic linkages, thereby degrading oligosaccharides and glycoconjugates, the structurally most diverse class of biopolymers. These efficient and highly specific catalysts play important roles in biological processes thus a detailed knowledge of glycosidase function is invaluable for understanding and controlling diseases and for industrial applications. The classification of this huge class of enzymes into families on the basis of amino acid sequence has provided a highly valuable tool for the analysis of structure–function relationships. Furthermore, the steady increase in three‐dimensional structural information is revealing further evolutionary relationships between glycosidase families. In addition to the majority of glycosidases that act via the classical Koshland mechanisms, a growing number of such enzymes that use unusual mechanisms are being uncovered. This confluence of bioinformatics, structural and mechanistic studies has greatly advanced glycosidase engineering and the development of specific glycosidase inhibitors.
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    • "Glycosyltransferases (GTases) catalyze the transfer of monosaccharide or oligosaccharides primarily from an activated sugar donor (UDP sugars) to various substrates, including carbohydrates, proteins and glycoproteins [14]. Their physiologic significance is further highlighted by the fact that they, along with glycosidases, make up 1 to 2% of the encoded genes in living organisms [15]. Recently, various reports have associated glycosyltransferases with the biogenesis of several virulence components of P. gingivalis like capsule [16], fimbriae [17], lipopolysaccharide [18] and gingipains [12]. "
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    ABSTRACT: Previously, we have reported that gingipain activity in Porphyromonas gingivalis, the major causative agent in adult periodontitis, is post-translationally regulated by the unique Vim proteins including VimF, a putative glycosyltransferase. To further characterize VimF, an isogenic mutant defective in this gene in a different P. gingivalis genetic background was evaluated. In addition, the recombinant VimF protein was used to further confirm its glycosyltransferase function. The vimF-defective mutant (FLL476) in the P. gingivalis ATCC 33277 genetic background showed a phenotype similar to that of the vimF-defective mutant (FLL95) in the P. gingivalis W83 genetic background. While hemagglutination was not detected and autoaggregation was reduced, biofilm formation was increased in FLL476. HeLa cells incubated with P. gingivalis FLL95 and FLL476 showed a 45% decrease in their invasive capacity. Antibodies raised against the recombinant VimF protein in E. coli immunoreacted only with the deglycosylated native VimF protein from P. gingivalis. In vitro glycosyltransferase activity for rVimF was observed using UDP-galactose and N-acetylglucosamine as donor and acceptor substrates, respectively. In the presence of rVimF and UDP-galactose, a 60 kDa protein from the extracellular fraction of FLL95 which was identified by mass spectrometry as Rgp gingipain, immunoreacted with the glycan specific mAb 1B5 antibody. Taken together, these results suggest the VimF glycoprotein is a galactosyltransferase that may be specific for gingipain glycosylation. Moreover, galatose is vital for the growing glycan chain.
    PLoS ONE 05/2013; 8(5):e63367. DOI:10.1371/journal.pone.0063367 · 3.23 Impact Factor
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