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Molecular basis for the glyphosate‐insensitivity of the reaction of 5‐enolpyruvylshikimate 3‐phosphate synthase with shikimate
Author(s) -
Priestman Melanie A.,
Healy Martha L.,
Funke Todd,
Becker Andreas,
Schönbrunn Ernst
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.09.066
Subject(s) - shikimate pathway , shikimic acid , biochemistry , chemistry , enzyme , atp synthase , stereochemistry
The shikimate pathway enzyme 5‐enolpyruvyl shikimate‐3‐phosphate synthase (EPSP synthase) has received attention in the past because it is the target of the broad‐spectrum herbicide glyphosate. The natural substrate of EPSP synthase is shikimate‐3‐phosphate. However, this enzyme can also utilize shikimate as substrate. Remarkably, this reaction is insensitive to inhibition by glyphosate. Crystallographic analysis of EPSP synthase from Escherichia coli , in complex with shikimate/glyphosate at 1.5 Å resolution, revealed that binding of shikimate induces changes around the backbone of the active site, which in turn impact the efficient binding of glyphosate. The implications from these findings with respect to the design of novel glyphosate‐insensitive EPSP synthase enzymes are discussed.