1YVE

ACETOHYDROXY ACID ISOMEROREDUCTASE COMPLEXED WITH NADPH, MAGNESIUM AND INHIBITOR IPOHA (N-HYDROXY-N-ISOPROPYLOXAMATE)

Summary for 1YVE

• Entry DOI: 10.2210/pdb1yve/pdb
• Descriptor: ACETOHYDROXY ACID ISOMEROREDUCTASE, MAGNESIUM ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: oxidoreductase, branched-chain amino acid biosynthesis, magnesium, nadp, chloroplast, transit peptide
• Biological source: Spinacia oleracea (spinach)
• Cellular location: Plastid, chloroplast: Q01292
• Total number of polymer chains: 4
• Total formula weight: 232053.17

Authors

Biou, V.,Dumas, R.,Cohen-Addad, C.,Douce, R.,Job, D.,Pebay-Peyroula, E. (deposition date: 1996-10-11, release date: 1997-09-04, Last modification date: 2024-02-14)

Primary citation

Biou, V.,Dumas, R.,Cohen-Addad, C.,Douce, R.,Job, D.,Pebay-Peyroula, E.
The crystal structure of plant acetohydroxy acid isomeroreductase complexed with NADPH, two magnesium ions and a herbicidal transition state analog determined at 1.65 A resolution.
EMBO J., 16:3405-3415, 1997

PubMed Abstract: Acetohydroxy acid isomeroreductase catalyzes the conversion of acetohydroxy acids into dihydroxy valerates. This reaction is the second in the synthetic pathway of the essential branched side chain amino acids valine and isoleucine. Because this pathway is absent from animals, the enzymes involved in it are good targets for a systematic search for herbicides. The crystal structure of acetohydroxy acid isomeroreductase complexed with cofactor NADPH, Mg2+ ions and a competitive inhibitor with herbicidal activity, N-hydroxy-N-isopropyloxamate, was solved to 1.65 A resolution and refined to an R factor of 18.7% and an R free of 22.9%. The asymmetric unit shows two functional dimers related by non-crystallographic symmetry. The active site, nested at the interface between the NADPH-binding domain and the all-helical C-terminus domain, shows a situation analogous to the transition state. It contains two Mg2+ ions interacting with the inhibitor molecule and bridged by the carboxylate moiety of an aspartate residue. The inhibitor-binding site is well adjusted to it, with a hydrophobic pocket and a polar region. Only 24 amino acids are conserved among known acetohydroxy acid isomeroreductase sequences and all of these are located around the active site. Finally, a 140 amino acid region, present in plants but absent from other species, was found to make up most of the dimerization domain.

PubMed: 9218783
DOI: 10.1093/emboj/16.12.3405

Experimental method

X-RAY DIFFRACTION (1.65 Å)