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Open Access Research article

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

Debanu Das12*, Alexey G Murzin3, Neil D Rawlings45, Robert D Finn6, Penelope Coggill45, Alex Bateman5, Adam Godzik17 and L Aravind8*

Author Affiliations

1 Joint Center for Structural Genomics, La Jolla, CA, USA

2 Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA, USA

3 MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK

4 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK

5 European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK

6 Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, VA, USA

7 Program on Bioinformatics and Systems Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA

8 National Center for Biotechnology Information, National Library of Medicine, Building 38A, Bethesda, MD, USA

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BMC Bioinformatics 2014, 15:75  doi:10.1186/1471-2105-15-75

Published: 19 March 2014

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.

Keywords:
CA_C2195; Peptidase; DUF4910; DUF2172; HTH_47; Structural genomics