5N6G

NerA from Agrobacterium radiobacter in complex with 2-phenylacrylic acid

Summary for 5N6G

• Entry DOI: 10.2210/pdb5n6g/pdb
• Descriptor: GTN Reductase, FLAVIN MONONUCLEOTIDE, 2-Phenylacrylic acid, ... (6 entities in total)
• Functional Keywords: old yellow enzyme, profen, ene-reductase, 2-phenylacrylic acid, oxidoreductase
• Biological source: Agrobacterium tumefaciens
• Total number of polymer chains: 1
• Total formula weight: 41927.21

Authors

Karuppiah, V.,Toogood, H.S.,Leys, D.,Scrutton, N.S. (deposition date: 2017-02-15, release date: 2017-05-17, Last modification date: 2024-01-17)

Primary citation

Waller, J.,Toogood, H.S.,Karuppiah, V.,Rattray, N.J.W.,Mansell, D.J.,Leys, D.,Gardiner, J.M.,Fryszkowska, A.,Ahmed, S.T.,Bandichhor, R.,Reddy, G.P.,Scrutton, N.S.
Structural insights into the ene-reductase synthesis of profens.
Org. Biomol. Chem., 15:4440-4448, 2017

PubMed Abstract: Reduction of double bonds of α,β-unsaturated carboxylic acids and esters by ene-reductases remains challenging and it typically requires activation by a second electron-withdrawing moiety, such as a halide or second carboxylate group. We showed that profen precursors, 2-arylpropenoic acids and their esters, were efficiently reduced by Old Yellow Enzymes (OYEs). The XenA and GYE enzymes showed activity towards acids, while a wider range of enzymes were active towards the equivalent methyl esters. Comparative co-crystal structural analysis of profen-bound OYEs highlighted key interactions important in determining substrate binding in a catalytically active conformation. The general utility of ene reductases for the synthesis of (R)-profens was established and this work will now drive future mutagenesis studies to screen for the production of pharmaceutically-active (S)-profens.

PubMed: 28485453
DOI: 10.1039/c7ob00163k

Experimental method

X-RAY DIFFRACTION (1.58 Å)