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 Das, Alexey G Murzin, Neil D Rawlings, Robert D Finn, Penelope Coggill, Alex Bateman, Adam Godzik, L Aravind
2014 BMC Bioinformatics  
Recent Work 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. Permalink https://escholarship.org/uc/item/4107q93s Journal BMC bioinformatics, 15(1) 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
more » ... . 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.
doi:10.1186/1471-2105-15-75 pmid:24646163 pmcid:PMC4000134 fatcat:jfh5gbwpefgr3d6axtopuhexj4