Dataset Information

Structure- and context-based analysis of the GxGYxYP family reveals a new putative class of glycoside hydrolase.

ABSTRACT: BACKGROUND:Gut microbiome metagenomics has revealed many protein families and domains found largely or exclusively in that environment. Proteins containing the GxGYxYP domain are over-represented in the gut microbiota, and are found in Polysaccharide Utilization Loci in the gut symbiont Bacteroides thetaiotaomicron, suggesting their involvement in polysaccharide metabolism, but little else is known of the function of this domain. RESULTS:Genomic context and domain architecture analyses support a role for the GxGYxYP domain in carbohydrate metabolism. Sparse occurrences in eukaryotes are the result of lateral gene transfer. The structure of the GxGYxYP domain-containing protein encoded by the BT2193 locus reveals two structural domains, the first composed of three divergent repeats with no recognisable homology to previously solved structures, the second a more familiar seven-stranded ?/? barrel. Structure-based analyses including conservation mapping localise a presumed functional site to a cleft between the two domains of BT2193. Matching to a catalytic site template from a GH9 cellulase and other analyses point to a putative catalytic triad composed of Glu272, Asp331 and Asp333. CONCLUSIONS:We suggest that GxGYxYP-containing proteins constitute a novel glycoside hydrolase family of as yet unknown specificity.

SUBMITTER: Rigden DJ

PROVIDER: S-EPMC4071793 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Structure- and context-based analysis of the GxGYxYP family reveals a new putative class of glycoside hydrolase.

Rigden Daniel J DJ Eberhardt Ruth Y RY Gilbert Harry J HJ Xu Qingping Q Chang Yuanyuan Y Godzik Adam A

BMC bioinformatics 20140617

<h4>Background</h4>Gut microbiome metagenomics has revealed many protein families and domains found largely or exclusively in that environment. Proteins containing the GxGYxYP domain are over-represented in the gut microbiota, and are found in Polysaccharide Utilization Loci in the gut symbiont Bacteroides thetaiotaomicron, suggesting their involvement in polysaccharide metabolism, but little else is known of the function of this domain.<h4>Results</h4>Genomic context and domain architecture ana ...[more]

PMID: 24938123

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Project description:Glycoside hydrolase (GH) family 29 consists solely of ?-L-fucosidases. These enzymes catalyse the hydrolysis of glycosidic bonds. Here, the structure of GH29_0940, a protein cloned from metagenomic DNA from the rumen of a cow, has been solved, which reveals a multi-domain arrangement that has only recently been identified in bacterial GH29 enzymes. The microbial species that provided the source of this enzyme is unknown. This enzyme contains a second carbohydrate-binding domain at its C-terminal end in addition to the typical N-terminal catalytic domain and carbohydrate-binding domain arrangement of GH29-family proteins. GH29_0940 is a monomer and its overall structure consists of an N-terminal TIM-barrel-like domain, a central ?-sandwich domain and a C-terminal ?-sandwich domain. The TIM-barrel-like catalytic domain exhibits a (?/?)8/7 arrangement in the core instead of the typical (?/?)8 topology, with the `missing' ?-helix replaced by a long meandering loop that `closes' the barrel structure and suggests a high degree of structural flexibility in the catalytic core. This feature was also noted in all six other structures of GH29 enzymes that have been deposited in the PDB. Based on sequence and structural similarity, the residues Asp162 and Glu220 are proposed to serve as the catalytic nucleophile and the proton donor, respectively. Like other GH29 enzymes, the GH29_0940 structure shows five strictly conserved residues in the catalytic pocket. The structure shows two glycerol molecules in the active site, which have also been observed in other GH29 structures, suggesting that the enzyme catalyses the hydrolysis of small carbohydrates. The two binding domains are classed as family 32 carbohydrate-binding modules (CBM32). These domains have residues involved in ligand binding in the loop regions at the edge of the ?-sandwich. The predicted substrate-binding residues differ between the modules, suggesting that different modules bind to different groups on the substrate(s). Enzymes that possess multiple copies of CBMs are thought to have a complex mechanism of ligand recognition. Defined electron density identifying a long 20-amino-acid hydrophilic loop separating the two CBMs was observed. This suggests that the additional C-terminal domain may have a dynamic range of movement enabled by the loop, allowing a unique mode of action for a GH29 enzyme that has not been identified previously.

Dataset Information

Structure- and context-based analysis of the GxGYxYP family reveals a new putative class of glycoside hydrolase.

Publications

Structure- and context-based analysis of the GxGYxYP family reveals a new putative class of glycoside hydrolase.

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