Local comparison of protein structures highlights cases of convergent evolution in analogous functional sites

Background: We performed an exhaustive search for local structural similarities in an ensemble of non-redundant protein functional sites. With the purpose of finding new examples of convergent evolution, we selected only those matching sites composed of structural regions whose residue order is inverted in the relative protein sequences. Results: A novel case of local analogy was detected between members of the ABC transporter and of the HprK/P families in their ATP binding site. This case cannot be derived by events of circular permutation since the residues of one of the region pairs are located in reverse order in the sequence of the two protein families. One of the analogous binding sites, the one identified in HprK/P, is known to also bind pyrophosphate, which is used as preferred energy source in its kinase and phosphorylase activity. Conclusion: The discovery of this striking molecular similarity, also associated to a functional similarity, may help in suggesting new experiments aimed at a deeper understanding of members of the ABC transporter family known to be involved in many serious human diseases.