PROSITE documentation PDOC51850
KARI N- and C-terminal domains profiles


Ketol-acid reductoisomerase (KARI; EC, also known as acetohydroxy acid isomeroreductase (AHIR or AHAIR), catalyzes the conversion of acetohydroxy acids into dihydroxy valerates in the second step of the biosynthetic pathway for the essential branched-chain amino acids valine, leucine, and isoleucine. KARI catalyzes an unusual two-step reaction consisting 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-dependent reduction 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. KARIs are divided into two classes on the basis of sequence length and oligomerization state. Class I KARIs are ~340 amino acid residues in length and include all fungal KARIs, whereas class II KARIs are ~490 residues long and include all plant KARIs. Bacterial KARIs can be either class I or class II. KARIs are composed of two types of domains, an N-terminal Rossmann fold domain and one or two C-terminal knotted domains. Two intertwinned knotted domains are required for function, and in the short-chain or class I KARIs, each polypeptide chain has one knotted domain. As a result, dimerization of two monomers forms two complete KARI active sites. In the long-chain or class II KARIs, a duplication of the knotted domain has occurred and, as a result, the protein does not require dimerization to complete its active site [1,2,3,4,5,6].

The α/β KARI N-terminal Rossmann fold domain consists of a nine-stranded mixed β-sheet with flanking α-helices on both sides of the β-sheet (see <PDB:1NP3>) [1,2,3,4,5].

The α-helical KARI C-terminal knotted domain can be described as a six-helix core in which helices coil like cable threads around each other, thus forming a bundle (see <PDB:1YVE>) [1,2,3,4,5].

The profiles we developed cover the entire KARI N- and C-terminal domains.

Last update:

January 2018 / First entry.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

KARI_C, PS51851; KARI C-terminal domain profile  (MATRIX)

KARI_N, PS51850; KARI N-terminal domain profile  (MATRIX)


1AuthorsBiou V. Dumas R. Cohen-Addad C. Douce R. Job D. Pebay-Peyroula E.
TitleThe 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.
SourceEMBO J. 16:3405-3415(1997).
PubMed ID9218783

2AuthorsDumas R. Biou V. Halgand F. Douce R. Duggleby R.G.
TitleEnzymology, structure, and dynamics of acetohydroxy acid isomeroreductase.
SourceAcc. Chem. Res. 34:399-408(2001).
PubMed ID11352718

3AuthorsAhn H.J. Eom S.J. Yoon H.-J. Lee B.I. Cho H. Suh S.W.
TitleCrystal structure of class I acetohydroxy acid isomeroreductase from Pseudomonas aeruginosa.
SourceJ. Mol. Biol. 328:505-515(2003).
PubMed ID12691757

4AuthorsTyagi R. Duquerroy S. Navaza J. Guddat L.W. Duggleby R.G.
TitleThe crystal structure of a bacterial class II ketol-acid reductoisomerase: domain conservation and evolution.
SourceProtein Sci. 14:3089-3100(2005).
PubMed ID16322583

5AuthorsCahn J.K.B. Brinkmann-Chen S. Spatzal T. Wiig J.A. Buller A.R. Einsle O. Hu Y. Ribbe M.W. Arnold F.H.
TitleCofactor specificity motifs and the induced fit mechanism in class I ketol-acid reductoisomerases.
SourceBiochem. J. 468:475-484(2015).
PubMed ID25849365

6AuthorsCahn J.K.B. Brinkmann-Chen S. Buller A.R. Arnold F.H.
TitleArtificial domain duplication replicates evolutionary history of ketol-acid reductoisomerases.
SourceProtein. Sci. 25:1241-1248(2016).
PubMed ID26644020

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