PDBsum entry 1g6t

Transferase

PDB id: 1g6t

Contents

Protein chain

427 a.a. *

Ligands

PO4

S3P

FMT ×13

Waters ×555

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Interaction of the herbicide glyphosate with its target enzyme 5-Enolpyruvylshikimate 3-Phosphate synthase in atomic detail.

Authors

E.Schönbrunn, S.Eschenburg, W.A.Shuttleworth, J.V.Schloss, N.Amrhein, J.N.Evans, W.Kabsch.

Ref.

Proc Natl Acad Sci U S A, 2001, 98, 1376-1380. [DOI no: 10.1073/pnas.98.4.1376]

PubMed id

11171958

Abstract

Biosynthesis of aromatic amino acids in plants, many bacteria, and microbes relies on the enzyme 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase, a prime target for drugs and herbicides. We have identified the interaction of EPSP synthase with one of its two substrates (shikimate 3-phosphate) and with the widely used herbicide glyphosate by x-ray crystallography. The two-domain enzyme closes on ligand binding, thereby forming the active site in the interdomain cleft. Glyphosate appears to occupy the binding site of the second substrate of EPSP synthase (phosphoenol pyruvate), mimicking an intermediate state of the ternary enzyme.substrates complex. The elucidation of the active site of EPSP synthase and especially of the binding pattern of glyphosate provides a valuable roadmap for engineering new herbicides and herbicide-resistant crops, as well as new antibiotic and antiparasitic drugs.

Figure 1.
Fig. 1. Cartoon of EPSP synthase in the open and closed conformation. Top domain, residues 20-240; bottom domain, residues 1-19 plus 241-427. (a) Unliganded state (open) as reconstructed from the deposited -carbon atoms (Protein Data Bank entry code 1EPS). (b) Liganded state (closed). S3P and glyphosate are shown as ball-and-stick models in green and magenta, respectively. Drawn with BOBSCRIPT (24).

Figure 3.
Fig. 3. Schematic representation of ligand binding in the EPSP synthase·S3P·glyphosate complex. Ligands are drawn in bold lines. Dashed lines indicate hydrogen bonds and ionic interactions. Strictly conserved residues are highlighted by bold labels. Protein atoms are labeled according to the Protein Data Bank nomenclature. Circled labels W1 to W4 designate solvent molecules. Hydrophobic interactions between S3P and Tyr-200 are omitted.