A Novel Superfamily Containing the β-Grasp Fold Involved in Binding Diverse Soluble Ligands
Burroughs, A. Maxwell
Iyer, Lakshminarayan M.
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Citation (published version)Burroughs, A. Maxwell, S. Balaji, Lakshminarayan M. Iyer, L. Aravind. "A novel superfamily containing the β-grasp fold involved in binding diverse soluble ligands" Biology Direct 2:4. (2007)
BACKGROUND. Domains containing the β-grasp fold are utilized in a great diversity of physiological functions but their role, if any, in soluble or small molecule ligand recognition is poorly studied. RESULTS. Using sensitive sequence and structure similarity searches we identify a novel superfamily containing the β-grasp fold. They are found in a diverse set of proteins that include the animal vitamin B12 uptake proteins transcobalamin and intrinsic factor, the bacterial polysaccharide export proteins, the competence DNA receptor ComEA, the cob(I)alamin generating enzyme PduS and the Nqo1 subunit of the respiratory electron transport chain. We present evidence that members of this superfamily are likely to bind a range of soluble ligands, including B12. There are two major clades within this superfamily, namely the transcobalamin-like clade and the Nqo1-like clade. The former clade is typified by an insert of a β-hairpin after the helix of the β-grasp fold, whereas the latter clade is characterized by an insert between strands 4 and 5 of the core fold. CONCLUSION. Members of both clades within this superfamily are predicted to interact with ligands in a similar spatial location, with their specific inserts playing a role in the process. Both clades are widely represented in bacteria suggesting that this superfamily was derived early in bacterial evolution. The animal lineage appears to have acquired the transcobalamin-like proteins from low GC Gram-positive bacteria, and this might be correlated with the emergence of the ability to utilize B12 produced by gut bacteria. REVIEWERS. This article was reviewed by Andrei Osterman, Igor Zhulin, and Arcady Mushegian.
RightsCopyright 2007 Burroughs et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.