| Title: |
Mirror-image packing provides a molecular basis for the nanomolar equipotency of enantiomers of an experimental herbicide |
| Authors: |
Bisson, Claudine; Britton, K. Linda; Sedelnikova, Svetlana E.; Rodgers, H. Fiona; Eadsforth, Thomas C.; Viner, Russell C.; Hawkes, Tim R.; Baker, Patrick J.; Rice, David W. |
| Source: |
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 2016, 'Mirror-image packing provides a molecular basis for the nanomolar equipotency of enantiomers of an experimental herbicide', Angewandte Chemie International Edition, vol. 55, no. 43, pp. 13485-13489. https://doi.org/10.1002/anie.201607185 |
| Publication Year: |
2016 |
| Collection: |
Discovery - University of Dundee Online Publications |
| Subject Terms: |
chirality; drug design; enantioselectivity; inhibitors; structural biology |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
1433-7851; 1521-3773 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/27717128; info:eu-repo/semantics/altIdentifier/pissn/1433-7851; info:eu-repo/semantics/altIdentifier/eissn/1521-3773 |
| DOI: |
10.1002/anie.201607185 |
| Availability: |
https://discovery.dundee.ac.uk/en/publications/20d992e4-f447-4be3-8ba0-51d2947e772e; https://doi.org/10.1002/anie.201607185; https://discovery.dundee.ac.uk/ws/files/10531223/Bisson_et_al_2016_Angewandte_Chemie_International_Edition.pdf |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.5FAE5B29 |
| Database: |
BASE |