title: Structural genomics analysis of uncharacterized protein families overrepresented in human gut bacteria identifies a novel glycoside hydrolase.
abstract: BACKGROUND
  Bacteroides spp. form a significant part of our gut microbiome and are well known for optimized metabolism of diverse polysaccharides. Initial analysis of the archetypal Bacteroides thetaiotaomicron genome identified 172 glycosyl hydrolases and a large number of uncharacterized proteins associated with polysaccharide metabolism.
  
  
  RESULTS
  BT_1012 from Bacteroides thetaiotaomicron VPI-5482 is a protein of unknown function and a member of a large protein family consisting entirely of uncharacterized proteins. Initial sequence analysis predicted that this protein has two domains, one on the N- and one on the C-terminal. A PSI-BLAST search found over 150 full length and over 90 half size homologs consisting only of the N-terminal domain. The experimentally determined three-dimensional structure of the BT_1012 protein confirms its two-domain architecture and structural analysis of both domains suggests their specific functions. The N-terminal domain is a putative catalytic domain with significant similarity to known glycoside hydrolases, the C-terminal domain has a beta-sandwich fold typically found in C-terminal domains of other glycosyl hydrolases, however these domains are typically involved in substrate binding. We describe the structure of the BT_1012 protein and discuss its sequence-structure relationship and their possible functional implications.
  
  
  CONCLUSIONS
  Structural and sequence analyses of the BT_1012 protein identifies it as a glycosyl hydrolase, expanding an already impressive catalog of enzymes involved in polysaccharide metabolism in Bacteroides spp. Based on this we have renamed the Pfam families representing the two domains found in the BT_1012 protein, PF13204 and PF12904, as putative glycoside hydrolase and glycoside hydrolase-associated C-terminal domain respectively.
authors.forename: Anna
authors.initials: A
authors.lastname: Sheydina
authors.forename: Ruth Y
authors.initials: RY
authors.lastname: Eberhardt
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rigden
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chang
authors.forename: Zhanwen
authors.initials: Z
authors.lastname: Li
authors.forename: Christian C
authors.initials: CC
authors.lastname: Zmasek
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Axelrod
authors.affiliation: Joint Center for Structural Genomics, 10550 North Torrey Pines Road, BCC-206, La Jolla, California 92037, USA. adam@sanfordburnham.org.
authors.forename: Adam
authors.initials: A
authors.lastname: Godzik
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D001439:Bacteroides / Q000201:enzymology; D019295:Computational Biology; D041981:Gastrointestinal Tract / Q000382:microbiology; D023281:Genomics; D006026:Glycoside Hydrolases / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D017434:Protein Structure, Tertiary
chemical_list: D001426:Bacterial Proteins; D006026:Glycoside Hydrolases
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