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Structure- and context-based analysis of the GxGYxYP family reveals a new putative class of Glycoside Hydrolase

Lookup NU author(s): Emeritus Professor Harry Gilbert



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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 beta/alpha 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.

Publication metadata

Author(s): Rigden DJ, Eberhardt RY, Gilbert HJ, Xu QP, Chang YY, Godzik A

Publication type: Article

Publication status: Published

Journal: BMC Bioinformatics

Year: 2014

Volume: 15

Online publication date: 17/06/2014

Acceptance date: 10/06/2014

Date deposited: 29/08/2014

ISSN (electronic): 1471-2105

Publisher: BioMed Central Ltd.


DOI: 10.1186/1471-2105-15-196


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Funder referenceFunder name
DOE Office of Biological and Environmental Research
Howard Hughes Medical Institute
IIS-1153617National Science Foundation
IIS-0646708National Science Foundation
P41GM103393National Institutes of Health, National Institute of General Medical Sciences
U54 GM094586National Institute of General Medical Sciences of the National Institutes of Health (NIH)
U54 GM094586-03NIH
WT077044/Z/05/ZWellcome Trust