5EL9

A. thaliana IGPD2 in complex with the triazole-phosphonate inhibitor, (S)-C348, to 1.1A resolution

Summary for 5EL9

• Entry DOI: 10.2210/pdb5el9/pdb
• Descriptor: Imidazoleglycerol-phosphate dehydratase 2, chloroplastic, MANGANESE (II) ION, [(2S)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl]phosphonic acid, ... (6 entities in total)
• Functional Keywords: herbicide discovery, histidine biosynthesis, inhibitor complex, dehydratase, lyase
• Biological source: Arabidopsis thaliana (Mouse-ear cress)
• Cellular location: Plastid, chloroplast : O23346
• Total number of polymer chains: 1
• Total formula weight: 23264.75

Authors

Bisson, C.,Britton, K.L.,Sedelnikova, S.E.,Rodgers, H.F.,Eadsforth, T.C.,Viner, R.C.,Hawkes, T.R.,Baker, P.J.,Rice, D.W. (deposition date: 2015-11-04, release date: 2016-10-05, Last modification date: 2024-01-10)

Primary citation

Bisson, C.,Britton, K.L.,Sedelnikova, S.E.,Rodgers, H.F.,Eadsforth, T.C.,Viner, R.C.,Hawkes, T.R.,Baker, P.J.,Rice, D.W.
Mirror-Image Packing Provides a Molecular Basis for the Nanomolar Equipotency of Enantiomers of an Experimental Herbicide.
Angew.Chem.Int.Ed.Engl., 55:13485-13489, 2016

PubMed Abstract: Programs of drug discovery generally exploit one enantiomer of a chiral compound for lead development following the principle that enantiomer recognition is central to biological specificity. However, chiral promiscuity has been identified for a number of enzyme families, which have shown that mirror-image packing can enable opposite enantiomers to be accommodated in an enzyme's active site. Reported here is a series of crystallographic studies of complexes between an enzyme and a potent experimental herbicide whose chiral center forms an essential part of the inhibitor pharmacophore. Initial studies with a racemate at 1.85 Å resolution failed to identify the chirality of the bound inhibitor, however, by extending the resolution to 1.1 Å and by analyzing high-resolution complexes with the enantiopure compounds, we determined that both enantiomers make equivalent pseudosymmetric interactions in the active site, thus mimicking an achiral reaction intermediate.

PubMed: 27717128
DOI: 10.1002/anie.201607185

Experimental method

X-RAY DIFFRACTION (1.1 Å)