3EA4

Arabidopsis thaliana acetohydroxyacid synthase in complex with monosulfuron-ester

Summary for 3EA4

• Entry DOI: 10.2210/pdb3ea4/pdb
• Related: 1YBH 1YHY 1YHZ 1YI1 1YIO 1Z8N 3E9Y
• Descriptor: Acetolactate synthase, chloroplastic, methyl 2-{[(4-methylpyrimidin-2-yl)carbamoyl]sulfamoyl}benzoate, FLAVIN-ADENINE DINUCLEOTIDE-N5-ISOBUTYL KETONE, ... (7 entities in total)
• Functional Keywords: fad and thdp dependent enzyme, amino-acid biosynthesis, branched-chain amino acid biosynthesis, chloroplast, fad, flavoprotein, herbicide resistance, magnesium, metal-binding, thiamine pyrophosphate, transferase, transit peptide
• Biological source: Arabidopsis thaliana (mouse-ear cress)
• Cellular location: Plastid, chloroplast : P17597
• Total number of polymer chains: 1
• Total formula weight: 65744.87

Authors

Guddat, L.W.,Wang, J.-G.,Li, Z.-M. (deposition date: 2008-08-24, release date: 2009-03-31, Last modification date: 2024-11-13)

Primary citation

Wang, J.-G.,Lee, P.K.,Dong, Y.-H.,Pang, S.S.,Duggleby, R.G.,Li, Z.-M.,Guddat, L.W.
Crystal structures of two novel sulfonylurea herbicides in complex with Arabidopsis thaliana acetohydroxyacid synthase.
Febs J., 276:1282-1290, 2009

PubMed Abstract: Acetohydroxyacid synthase (AHAS; EC 2.2.1.6) is the first enzyme in the biosynthetic pathway of the branched-chain amino acids. It catalyzes the conversion of two molecules of pyruvate into 2-acetolactate or one molecule of pyruvate and one molecule of 2-ketobutyrate into 2-aceto-2-hydroxybutyrate. AHAS requires the cofactors thiamine diphosphate (ThDP), Mg(2+) and FAD for activity. The herbicides that target this enzyme are effective in protecting a broad range of crops from weed species. However, resistance in the field is now a serious problem worldwide. To address this, two new sulfonylureas, monosulfuron and monosulfuron ester, have been developed as commercial herbicides in China. These molecules differ from the traditional sulfonylureas in that the heterocyclic ring attached to the nitrogen atom of the sulfonylurea bridge is monosubstituted rather than disubstituted. The structures of these compounds in complex with the catalytic subunit of Arabidopsis thaliana AHAS have been determined to 3.0 and 2.8 A, respectively. In both complexes, these molecules are bound in the tunnel leading to the active site, such that the sole substituent of the heterocyclic ring is buried deepest and oriented towards the ThDP. Unlike the structures of Arabidopsis thaliana AHAS in complex with the classic disubstituted sulfonylureas, where ThDP is broken, this cofactor is intact and present most likely as the hydroxylethyl intermediate.

PubMed: 19187232
DOI: 10.1111/j.1742-4658.2009.06863.x

Experimental method

X-RAY DIFFRACTION (2.8 Å)