PDBsum entry 1z8n

Transferase

PDB id: 1z8n

Contents

Protein chain

582 a.a.

Ligands

1IQ ×2

NHE

FAD

TPP

Metals

_MG

Waters ×287

References listed in PDB file

Key reference

Title

Herbicide-Binding sites revealed in the structure of plant acetohydroxyacid synthase.

Authors

J.A.Mccourt, S.S.Pang, J.King-Scott, L.W.Guddat, R.G.Duggleby.

Ref.

Proc Natl Acad Sci U S A, 2006, 103, 569-573. [DOI no: 10.1073/pnas.0508701103]

PubMed id

16407096

Abstract

The sulfonylureas and imidazolinones are potent commercial herbicide families. They are among the most popular choices for farmers worldwide, because they are nontoxic to animals and highly selective. These herbicides inhibit branched-chain amino acid biosynthesis in plants by targeting acetohydroxyacid synthase (AHAS, EC 2.2.1.6). This report describes the 3D structure of Arabidopsis thaliana AHAS in complex with five sulfonylureas (to 2.5 A resolution) and with the imidazolinone, imazaquin (IQ; 2.8 A). Neither class of molecule has a structure that mimics the substrates for the enzyme, but both inhibit by blocking a channel through which access to the active site is gained. The sulfonylureas approach within 5 A of the catalytic center, which is the C2 atom of the cofactor thiamin diphosphate, whereas IQ is at least 7 A from this atom. Ten of the amino acid residues that bind the sulfonylureas also bind IQ. Six additional residues interact only with the sulfonylureas, whereas there are two residues that bind IQ but not the sulfonylureas. Thus, the two classes of inhibitor occupy partially overlapping sites but adopt different modes of binding. The increasing emergence of resistant weeds due to the appearance of mutations that interfere with the inhibition of AHAS is now a worldwide problem. The structures described here provide a rational molecular basis for understanding these mutations, thus allowing more sophisticated AHAS inhibitors to be developed. There is no previously described structure for any plant protein in complex with a commercial herbicide.

Figure 1.
Fig. 1. The overall fold of AtAHAS. (A) The tetrameric structure with each monomer colored separately. (B) A single subunit. The individual domains (86-280), (281-451), and (463-639) are colored gold, red, and blue, respectively. The C-terminal tail (646-668) is colored green. ThDP, Mg2+, FAD, and IQ are shown as ball-and-stick models and are colored red, dark blue, cyan, and yellow, respectively.

Figure 4.
Fig. 4. Stereoview of the conformational adjustments in the AtAHAS herbicide-binding sites. (A) IQ. (B) CE. Herbicide carbon atoms are colored green. AtAHAS carbon atoms are colored gray, whereas the color scheme for noncarbon atoms is as described in Fig. 2. ' indicates that these residues are from the neighboring subunit.