Prediction and assignment of function for a divergent N-succinyl amino acid racemase. Academic Article uri icon


  • The protein databases contain many proteins with unknown function. A computational approach for predicting ligand specificity that requires only the sequence of the unknown protein would be valuable for directing experiment-based assignment of function. We focused on a family of unknown proteins in the mechanistically diverse enolase superfamily and used two approaches to assign function: (i) enzymatic assays using libraries of potential substrates, and (ii) in silico docking of the same libraries using a homology model based on the most similar (35% sequence identity) characterized protein. The results matched closely; an experimentally determined structure confirmed the predicted structure of the substrate-liganded complex. We assigned the N-succinyl arginine/lysine racemase function to the family, correcting the annotation (L-Ala-D/L-Glu epimerase) based on the function of the most similar characterized homolog. These studies establish that ligand docking to a homology model can facilitate functional assignment of unknown proteins by restricting the identities of the possible substrates that must be experimentally tested.

published proceedings

  • Nat Chem Biol

altmetric score

  • 4

author list (cited authors)

  • Song, L., Kalyanaraman, C., Fedorov, A. A., Fedorov, E. V., Glasner, M. E., Brown, S., ... Gerlt, J. A.

citation count

  • 88

complete list of authors

  • Song, Ling||Kalyanaraman, Chakrapani||Fedorov, Alexander A||Fedorov, Elena V||Glasner, Margaret E||Brown, Shoshana||Imker, Heidi J||Babbitt, Patricia C||Almo, Steven C||Jacobson, Matthew P||Gerlt, John A

publication date

  • January 2007