5DNX

Crystal structure of IGPD from Pyrococcus furiosus in complex with (R)-C348

Summary for 5DNX

• Entry DOI: 10.2210/pdb5dnx/pdb
• Related: 5DNL
• Descriptor: Imidazoleglycerol-phosphate dehydratase, MANGANESE (II) ION, [(2R)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl]phosphonic acid, ... (4 entities in total)
• Functional Keywords: inhibitor, complex, dehydratase, lyase, cytoplasmic
• Biological source: Pyrococcus furiosus
• Cellular location: Cytoplasm : P58880
• Total number of polymer chains: 3
• Total formula weight: 60245.42

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: 2015-09-10, release date: 2016-10-05, Last modification date: 2024-05-08)

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 (1.8 Å)