Ketol-acid reductoisomerase (KARI; EC 220.127.116.11), 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
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.
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