3IJL

Structure of dipeptide epimerase from Bacteroides thetaiotaomicron complexed with L-Pro-D-Glu; nonproductive substrate binding.

Summary for 3IJL

• Entry DOI: 10.2210/pdb3ijl/pdb
• Related: 3IJI 3IJQ
• Descriptor: Muconate cycloisomerase, PROLINE, D-GLUTAMIC ACID, ... (5 entities in total)
• Functional Keywords: enolase superfamily, dipeptide epimerase, l-pro-d-glu, nonproductive binding, isomerase
• Biological source: Bacteroides thetaiotaomicron
• Total number of polymer chains: 2
• Total formula weight: 75639.87

Authors

Fedorov, A.A.,Fedorov, E.V.,Lukk, T.,Gerlt, J.A.,Almo, S.C. (deposition date: 2009-08-04, release date: 2010-07-21, Last modification date: 2023-09-06)

Primary citation

Lukk, T.,Sakai, A.,Kalyanaraman, C.,Brown, S.D.,Imker, H.J.,Song, L.,Fedorov, A.A.,Fedorov, E.V.,Toro, R.,Hillerich, B.,Seidel, R.,Patskovsky, Y.,Vetting, M.W.,Nair, S.K.,Babbitt, P.C.,Almo, S.C.,Gerlt, J.A.,Jacobson, M.P.
Homology models guide discovery of diverse enzyme specificities among dipeptide epimerases in the enolase superfamily.
Proc.Natl.Acad.Sci.USA, 109:4122-4127, 2012

PubMed Abstract: The rapid advance in genome sequencing presents substantial challenges for protein functional assignment, with half or more of new protein sequences inferred from these genomes having uncertain assignments. The assignment of enzyme function in functionally diverse superfamilies represents a particular challenge, which we address through a combination of computational predictions, enzymology, and structural biology. Here we describe the results of a focused investigation of a group of enzymes in the enolase superfamily that are involved in epimerizing dipeptides. The first members of this group to be functionally characterized were Ala-Glu epimerases in Eschericiha coli and Bacillus subtilis, based on the operon context and enzymological studies; these enzymes are presumed to be involved in peptidoglycan recycling. We have subsequently studied more than 65 related enzymes by computational methods, including homology modeling and metabolite docking, which suggested that many would have divergent specificities;, i.e., they are likely to have different (unknown) biological roles. In addition to the Ala-Phe epimerase specificity reported previously, we describe the prediction and experimental verification of: (i) a new group of presumed Ala-Glu epimerases; (ii) several enzymes with specificity for hydrophobic dipeptides, including one from Cytophaga hutchinsonii that epimerizes D-Ala-D-Ala; and (iii) a small group of enzymes that epimerize cationic dipeptides. Crystal structures for certain of these enzymes further elucidate the structural basis of the specificities. The results highlight the potential of computational methods to guide experimental characterization of enzymes in an automated, large-scale fashion.

PubMed: 22392983
DOI: 10.1073/pnas.1112081109

Experimental method

X-RAY DIFFRACTION (1.5 Å)