PROSITE documentation PDOC51850KARI N- and C-terminal domains profiles
Ketol-acid reductoisomerase (KARI; EC 1.1.1.86), 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.
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PROSITE methods (with tools and information) covered by this documentation:
| 1 | Authors | Biou V. Dumas R. Cohen-Addad C. Douce R. Job D. Pebay-Peyroula E. |
| Title | 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. | |
| Source | EMBO J. 16:3405-3415(1997). | |
| PubMed ID | 9218783 | |
| DOI | 10.1093/emboj/16.12.3405 |
| 2 | Authors | Dumas R. Biou V. Halgand F. Douce R. Duggleby R.G. |
| Title | Enzymology, structure, and dynamics of acetohydroxy acid isomeroreductase. | |
| Source | Acc. Chem. Res. 34:399-408(2001). | |
| PubMed ID | 11352718 |
| 3 | Authors | Ahn H.J. Eom S.J. Yoon H.-J. Lee B.I. Cho H. Suh S.W. |
| Title | Crystal structure of class I acetohydroxy acid isomeroreductase from Pseudomonas aeruginosa. | |
| Source | J. Mol. Biol. 328:505-515(2003). | |
| PubMed ID | 12691757 |
| 4 | Authors | Tyagi R. Duquerroy S. Navaza J. Guddat L.W. Duggleby R.G. |
| Title | The crystal structure of a bacterial class II ketol-acid reductoisomerase: domain conservation and evolution. | |
| Source | Protein Sci. 14:3089-3100(2005). | |
| PubMed ID | 16322583 | |
| DOI | 10.1110/ps.051791305 |
| 5 | Authors | Cahn J.K.B. Brinkmann-Chen S. Spatzal T. Wiig J.A. Buller A.R. Einsle O. Hu Y. Ribbe M.W. Arnold F.H. |
| Title | Cofactor specificity motifs and the induced fit mechanism in class I ketol-acid reductoisomerases. | |
| Source | Biochem. J. 468:475-484(2015). | |
| PubMed ID | 25849365 | |
| DOI | 10.1042/BJ20150183 |
| 6 | Authors | Cahn J.K.B. Brinkmann-Chen S. Buller A.R. Arnold F.H. |
| Title | Artificial domain duplication replicates evolutionary history of ketol-acid reductoisomerases. | |
| Source | Protein. Sci. 25:1241-1248(2016). | |
| PubMed ID | 26644020 | |
| DOI | 10.1002/pro.2852 |
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