InterPro domain: IPR013116

Ketol-acid reductoisomerase (KARI; ( 1.1.1.86 )), also known as acetohydroxyacid isomeroreductase (AHIR or AHAIR), catalyzes the conversion ofacetohydroxy acids into dihydroxy valerates in the second step of thebiosynthetic pathway for the essential branched-chain amino acids valine,leucine, and isoleucine. KARI catalyzes an unusual two-step reactionconsisting of an alkyl migration in which the substrate, either 2-acetolactate(AL) or 2-aceto-2-hydroxybutarate (AHB), is converted to 3-hydoxy-3-methyl-2-oxobutyrate or 3-hydoxy-3-methyl-2-pentatonate, followed by a NADPH-dependentreduction to give 2,3-dihydroxy-3-isovalerate or 2,3-dihydroxy-3-methylvalerate respectively [ 1 , 2 , 3 , 4 , 5 , 6 ].

KARI is present only in bacteria, fungi, and plants, but not in animals. KARIsare divided into two classes on the basis of sequence length andoligomerization state. Class I KARIs are ~340 amino acid residues in lengthand include all fungal KARIs, whereas class II KARIs are ~490 residues longand include all plant KARIs. Bacterial KARIs can be either class I or classII. KARIs are composed of two types of domains, an N-terminal Rossmann folddomain and one or two C-terminal knotted domains. Two intertwinned knotteddomains are required for function, and in the short-chain or class I KARIs,each polypeptide chain has one knotted domain. As a result, dimerization oftwo monomers forms two complete KARI active sites. In the long-chain or classII KARIs, a duplication of the knotted domain has occurred and, as a result,the protein does not require dimerization to complete its active site[ 7 , 7 , 7 , 7 , 7 , 7 ].

The alpha/beta KARI N-terminal Rossmann fold domain consists of a nine-stranded mixed beta-sheet with flanking alpha-helices on both sides of the beta-sheet.

1. 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, 3405-15
2. Enzymology, structure, and dynamics of acetohydroxy acid isomeroreductase. Acc. Chem. Res. 34, 399-408
3. Crystal structure of class I acetohydroxy acid isomeroreductase from Pseudomonas aeruginosa. J. Mol. Biol. 328, 505-15
4. The crystal structure of a bacterial class II ketol-acid reductoisomerase: domain conservation and evolution. Protein Sci. 14, 3089-100
5. Cofactor specificity motifs and the induced fit mechanism in class I ketol-acid reductoisomerases. Biochem. J. 468, 475-84
6. Artificial domain duplication replicates evolutionary history of ketol-acid reductoisomerases. Protein Sci. 25, 1241-8