title: 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 β/α 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.
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Liverpool, UK. drigden@liv.ac.uk.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rigden
authors.forename: Ruth Y
authors.initials: RY
authors.lastname: Eberhardt
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Gilbert
authors.forename: Qingping
authors.initials: Q
authors.lastname: Xu
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chang
authors.forename: Adam
authors.initials: A
authors.lastname: Godzik
mesh_terms: D001439:Bacteroides / Q000737:chemistry / Q000201:enzymology; D055162:Biocatalysis; D006026:Glycoside Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein
chemical_list: D006026:Glycoside Hydrolases