Loss of quaternary structure is associated with rapid sequence divergence in the OSBS family Academic Article uri icon


  • The rate of protein evolution is determined by a combination of selective pressure on protein function and biophysical constraints on protein folding and structure. Determining the relative contributions of these properties is an unsolved problem in molecular evolution with broad implications for protein engineering and function prediction. As a case study, we examined the structural divergence of the rapidly evolving o-succinylbenzoate synthase (OSBS) family, which catalyzes a step in menaquinone synthesis in diverse microorganisms and plants. On average, the OSBS family is much more divergent than other protein families from the same set of species, with the most divergent family members sharing <15% sequence identity. Comparing 11 representative structures revealed that loss of quaternary structure and large deletions or insertions are associated with the family's rapid evolution. Neither of these properties has been investigated in previous studies to identify factors that affect the rate of protein evolution. Intriguingly, one subfamily retained a multimeric quaternary structure and has small insertions and deletions compared with related enzymes that catalyze diverse reactions. Many proteins in this subfamily catalyze both OSBS and N-succinylamino acid racemization (NSAR). Retention of ancestral structural characteristics in the NSAR/OSBS subfamily suggests that the rate of protein evolution is not proportional to the capacity to evolve new protein functions. Instead, structural features that are conserved among proteins with diverse functions might contribute to the evolution of new functions.

altmetric score

  • 1

author list (cited authors)

  • Odokonyero, D., Sakai, A., Patskovsky, Y., Malashkevich, V. N., Fedorov, A. A., Bonanno, J. B., ... Glasner, M. E.

citation count

  • 18

complete list of authors

  • Odokonyero, Denis||Sakai, Ayano||Patskovsky, Yury||Malashkevich, Vladimir N||Fedorov, Alexander A||Bonanno, Jeffrey B||Fedorov, Elena V||Toro, Rafael||Agarwal, Rakhi||Wang, Chenxi||Ozerova, Nicole DS||Yew, Wen Shan||Sauder, J Michael||Swaminathan, Subramanyam||Burley, Stephen K||Almo, Steven C||Glasner, Margaret E

publication date

  • June 2014