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- Title
Prediction and assignment of function for a divergent N-succinyl amino acid racemase.
- Authors
Ling Song; 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.
- Abstract
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.
- Publication
Nature Chemical Biology, 2007, Vol 3, Issue 8, p486
- ISSN
1552-4450
- Publication type
Academic Journal
- DOI
10.1038/nchembio.2007.11