3DEQ

Crystal structure of dipeptide epimerase from Thermotoga maritima complexed with L-Ala-L-Leu dipeptide

Summary for 3DEQ

• Entry DOI: 10.2210/pdb3deq/pdb
• Related: 3DER 3DES
• Descriptor: Muconate cycloisomerase, MAGNESIUM ION, ALANINE, ... (5 entities in total)
• Functional Keywords: dipeptide epimerase, thermotoga maritima, enzymatic function, isomerase
• Biological source: Thermotoga maritima MSB8
• Total number of polymer chains: 4
• Total formula weight: 155847.42

Authors

Fedorov, A.A.,Fedorov, E.V.,Imker, H.J.,Gerlt, J.A.,Almo, S.C. (deposition date: 2008-06-10, release date: 2008-11-25, Last modification date: 2024-03-13)

Primary citation

Kalyanaraman, C.,Imker, H.J.,Fedorov, A.A.,Fedorov, E.V.,Glasner, M.E.,Babbitt, P.C.,Almo, S.C.,Gerlt, J.A.,Jacobson, M.P.
Discovery of a dipeptide epimerase enzymatic function guided by homology modeling and virtual screening.
Structure, 16:1668-1677, 2008

PubMed Abstract: We have developed a computational approach to aid the assignment of enzymatic function for uncharacterized proteins that uses homology modeling to predict the structure of the binding site and in silico docking to identify potential substrates. We apply this method to proteins in the functionally diverse enolase superfamily that are homologous to the characterized L-Ala-D/L-Glu epimerase from Bacillus subtilis. In particular, a protein from Thermotoga martima was predicted to have different substrate specificity, which suggests that it has a different, but as yet unknown, biological function. This prediction was experimentally confirmed, resulting in the assignment of epimerase activity for L-Ala-D/L-Phe, L-Ala-D/L-Tyr, and L-Ala-D/L-His, whereas the enzyme is annotated incorrectly in GenBank as muconate cycloisomerase. Subsequently, crystal structures of the enzyme were determined in complex with three substrates, showing close agreement with the computational models and revealing the structural basis for the observed substrate selectivity.

PubMed: 19000819
DOI: 10.1016/j.str.2008.08.015

Experimental method

X-RAY DIFFRACTION (2.1 Å)