title: Structure and computational analysis of a novel protein with metallopeptidase-like and circularly permuted winged-helix-turn-helix domains reveals a possible role in modified polysaccharide biosynthesis.
abstract: BACKGROUND
  CA_C2195 from Clostridium acetobutylicum is a protein of unknown function. Sequence analysis predicted that part of the protein contained a metallopeptidase-related domain. There are over 200 homologs of similar size in large sequence databases such as UniProt, with pairwise sequence identities in the range of ~40-60%. CA_C2195 was chosen for crystal structure determination for structure-based function annotation of novel protein sequence space.
  
  
  RESULTS
  The structure confirmed that CA_C2195 contained an N-terminal metallopeptidase-like domain. The structure revealed two extra domains: an α+β domain inserted in the metallopeptidase-like domain and a C-terminal circularly permuted winged-helix-turn-helix domain.
  
  
  CONCLUSIONS
  Based on our sequence and structural analyses using the crystal structure of CA_C2195 we provide a view into the possible functions of the protein. From contextual information from gene-neighborhood analysis, we propose that rather than being a peptidase, CA_C2195 and its homologs might play a role in biosynthesis of a modified cell-surface carbohydrate in conjunction with several sugar-modification enzymes. These results provide the groundwork for the experimental verification of the function.
authors.affiliation: Joint Center for Structural Genomics, La Jolla, CA, USA. debanu@slac.stanford.edu.
authors.forename: Debanu
authors.initials: D
authors.lastname: Das
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Murzin
authors.forename: Neil D
authors.initials: ND
authors.lastname: Rawlings
authors.forename: Robert D
authors.initials: RD
authors.lastname: Finn
authors.forename: Penelope
authors.initials: P
authors.lastname: Coggill
authors.forename: Alex
authors.initials: A
authors.lastname: Bateman
authors.forename: Adam
authors.initials: A
authors.lastname: Godzik
authors.forename: L
authors.initials: L
authors.lastname: Aravind
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D046969:Clostridium acetobutylicum / Q000201:enzymology* / Q000235:genetics; D018360:Crystallography, X-Ray; D045726:Metalloproteases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D017434:Protein Structure, Tertiary
chemical_list: D001426:Bacterial Proteins; D045726:Metalloproteases