@article {45865, 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.}, journal = {BMC Bioinformatics}, volume = {15}, year = {2014}, month = {2014 Mar 19}, pages = {75}, 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 = {Bacterial Proteins, Clostridium acetobutylicum, Crystallography, X-Ray, Metalloproteases, Models, Molecular, Protein Structure, Tertiary}, issn = {1471-2105}, doi = {10.1186/1471-2105-15-75}, author = {Das, Debanu and Murzin, Alexey G and Rawlings, Neil D and Finn, Robert D and Coggill, Penelope and Bateman, Alex and Godzik, Adam and Aravind, L} } @article {6537, title = {Two Pfam protein families characterized by a crystal structure of protein lpg2210 from Legionella pneumophila.}, journal = {BMC Bioinformatics}, volume = {14}, year = {2013}, month = {2013 Sep 3}, pages = {265}, abstract = {

BACKGROUND: Every genome contains a large number of uncharacterized proteins that may encode entirely novel biological systems. Many of these uncharacterized proteins fall into related sequence families. By applying sequence and structural analysis we hope to provide insight into novel biology. RESULTS: We analyze a previously uncharacterized Pfam protein family called DUF4424 [Pfam:PF14415]. The recently solved three-dimensional structure of the protein lpg2210 from Legionella pneumophila provides the first structural information pertaining to this family. This protein additionally includes the first representative structure of another Pfam family called the YARHG domain [Pfam:PF13308]. The Pfam family DUF4424 adopts a 19-stranded beta-sandwich fold that shows similarity to the N-terminal domain of leukotriene A-4 hydrolase. The YARHG domain forms an all-helical domain at the C-terminus. Structure analysis allows us to recognize distant similarities between the DUF4424 domain and individual domains of M1 aminopeptidases and tricorn proteases, which form massive proteasome-like capsids in both archaea and bacteria. CONCLUSIONS: Based on our analyses we hypothesize that the DUF4424 domain may have a role in forming large, multi-component enzyme complexes. We suggest that the YARGH domain may play a role in binding a moiety in proximity with peptidoglycan, such as a hydrophobic outer membrane lipid or lipopolysaccharide.

}, issn = {1471-2105}, doi = {10.1186/1471-2105-14-265}, author = {Coggill, Penelope and Eberhardt, Ruth Y and Finn, Robert D and Chang, Yuanyuan and Jaroszewski, Lukasz and Godzik, Adam and Das, Debanu and Xu, Qingping and Axelrod, Herbert L and Aravind, L and Murzin, Alexey G and Bateman, Alex} }