Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

ketol-acid reductoisomerase By Reference

Ketol-acid reductoisomerase (KARI) is a Mg(2+) -dependent enzyme in the branched-chain amino acid biosynthesis pathway. KARI catalyses two steps in the biosynthesis of branched-chain amino acids. The reaction involves an Mg(II) dependent alkyl migration followed by an NADPH-dependent reduction of the 2-keto group.




• Summary
• Step 1
• Step 2
• Step 3
• Products

The reaction is initiated by a proton abstraction (by the hydroxide ion bridging the two metal ions), followed by a concerted isomerisation and hydride transfer. The two protons needed to protonate the product are proposed to be donated from the bridging water ligand and a conserved lysine

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
Asp	Q01292	315	1yve	244
Glu	Q01292	319	1yve	248
Lys	Q01292	252	1yve	181

Step Components

overall reactant used, proton transfer, overall product formed, intramolecular rearrangement, native state of cofactor regenerated, native state of enzyme regenerated, inferred reaction step, hydride transfer



Step 1.

A magnesium activated water molecule abstracts the proton from the alcohol, initiating a 1,2-alkyl shift with concomitant deprotonation of the conserved Lys252 residue.



Step 2.

NADPH eliminates a hydride ion, that is added to the newly formed carbonyl group, which in turn abstracts the proton from the magnesium bound water molecule, regenerating the bound hydroxide ion.



Step 3.

In an inferred return step, water donates a proton to the lysine to regenerate the enzyme's active site.



Products.

The products of the reaction.

View Reaction Mechanisms in M-CSA

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Citations

• Synthesis of isobutanol using acetate as sole carbon source in Escherichia coli.
• Mycoparasitism related targets of Tmk1 indicate stimulating regulatory functions of this MAP kinase in Trichoderma atroviride.
• Construction of a plasmid-free L-leucine overproducing Escherichia coli strain through reprogramming of the metabolic flux.
• Evaluation of Cell Responses of Saccharomyces cerevisiae under Cultivation Using Wheat Bran as a Nutrient Resource by Analyses of Growth Activities and Comprehensive Gene Transcription Levels
• Structural Rearrangements of a Dodecameric Ketol-Acid Reductoisomerase Isolated from a Marine Thermophilic Methanogen.
• System metabolic engineering of Escherichia coli W for the production of 2-ketoisovalerate using unconventional feedstock.
• Polyethylene Degradation by a Rhodococcous Strain Isolated from Naturally Weathered Plastic Waste Enrichment.
• Discovery of a Pyrimidinedione Derivative with Potent Inhibitory Activity against Mycobacterium tuberculosis Ketol-Acid Reductoisomerase.
• Comparative proteome profiles of Polygonatum cyrtonema Hua rhizomes (Rhizoma Ploygonati) in response to different levels of cadmium stress.
• Discovery, Synthesis and Evaluation of a Ketol-Acid Reductoisomerase Inhibitor.
• Optimal energy and redox metabolism in the cyanobacterium Synechocystis sp. PCC 6803.