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Literature summary for 2.6.1.42 extracted from

  • Amorim Franco, T.M.; Favrot, L.; Vergnolle, O.; Blanchard, J.S.
    Mechanism-based inhibition of the Mycobacterium tuberculosis branched-chain aminotransferase by D- and L-cycloserine (2017), ACS Chem. Biol., 12, 1235-1244 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.6.1.42

Crystallization (Commentary)

Crystallization (Comment) Organism
purified recombinant enzyme MtIlvE bound by inhibitor D-cycloserine and pyridoxamine (PMP), X-ray diffraction structure determination and analysis at 1.7 A resolution Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
D-cycloserine DCS, mechanism-based inhibition of the Mycobacterium tuberculosis branched-chain aminotransferase by D-cycloserine, mechanism and enzyme-bound three-dimensional structure with a role of residue C196, overview. Time and concentration-dependent inactivation. The structure of the covalent D-cycloserine-PMP adduct bound to MtIlvE reveals that the D-cycloserine ring is planar and aromatic Mycobacterium tuberculosis
L-Cycloserine LCS, mechanism-based inhibition of the Mycobacterium tuberculosis branched-chain aminotransferase by L-cycloserine, mchanism overview, time and concentration-dependent inactivation Mycobacterium tuberculosis
additional information L-cycloserine is a 10fold better inhibitor of Mycobacterium tuberculosis growth than D-cycloserine. Both the D-cycloserine and L-cycloserine-PMP complexes have the same mass, and are likely to be the same aromatized, isoxazole product, but the kinetics of formation of the MtIlvE D-cycloserine-PMP and MtIlvE L-cycloserine-PMP adducts are quite different. While the kinetics of the formation of the MtIlvE D-cycloserine-PMP complex can be fit to a single exponential, the formation of the MtIlvE L-cycloserine-PMP complex occurs in two steps. No inhibition of the enzyme by propargylglycine (an inhibitor of cystathionine gamma-synthase), by gabaculine (an inhibitor of GABA aminotransferase and ornithine decarboxylase) or by difluoromethylornithine (DFMO, the inhibitor of ornithine decarboxylase). Also gabapentin, a potent inhibitor of the cytosolic isozyme hBCATc, has no effect on the activity of MtIlvE Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-isoleucine + 2-oxoglutarate Mycobacterium tuberculosis
-
 3-methyl-2-oxopentanoate + L-glutamate
-
 r
L-isoleucine + 2-oxoglutarate Mycobacterium tuberculosis H37Rv
-
 3-methyl-2-oxopentanoate + L-glutamate
-
 r
L-leucine + 2-oxoglutarate Mycobacterium tuberculosis
-
 4-methyl-2-oxopentanoate + L-glutamate
-
 r
L-leucine + 2-oxoglutarate Mycobacterium tuberculosis H37Rv
-
 4-methyl-2-oxopentanoate + L-glutamate
-
 r
L-valine + 2-oxoglutarate Mycobacterium tuberculosis
-
 3-methyl-2-oxobutanoate + L-glutamate
-
 r
L-valine + 2-oxoglutarate Mycobacterium tuberculosis H37Rv
-
 3-methyl-2-oxobutanoate + L-glutamate
-
 r

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WQ75
-
-
Mycobacterium tuberculosis H37Rv P9WQ75
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-isoleucine + 2-oxoglutarate
-
 Mycobacterium tuberculosis 3-methyl-2-oxopentanoate + L-glutamate
-
 r
L-isoleucine + 2-oxoglutarate
-
 Mycobacterium tuberculosis H37Rv 3-methyl-2-oxopentanoate + L-glutamate
-
 r
L-leucine + 2-oxoglutarate
-
 Mycobacterium tuberculosis 4-methyl-2-oxopentanoate + L-glutamate
-
 r
L-leucine + 2-oxoglutarate
-
 Mycobacterium tuberculosis H37Rv 4-methyl-2-oxopentanoate + L-glutamate
-
 r
L-valine + 2-oxoglutarate
-
 Mycobacterium tuberculosis 3-methyl-2-oxobutanoate + L-glutamate
-
 r
L-valine + 2-oxoglutarate
-
 Mycobacterium tuberculosis H37Rv 3-methyl-2-oxobutanoate + L-glutamate
-
 r
additional information MtIlvE is an L-amino acid aminotransferase Mycobacterium tuberculosis ?
-
-
additional information MtIlvE is an L-amino acid aminotransferase Mycobacterium tuberculosis H37Rv ?
-
-

Subunits

Subunits Comment Organism
homodimer
-
 Mycobacterium tuberculosis

Synonyms

Synonyms Comment Organism
BcaT
-
 Mycobacterium tuberculosis
branched-chain aminotransferase
-
 Mycobacterium tuberculosis
IlvE
-
 Mycobacterium tuberculosis
MtIlvE
-
 Mycobacterium tuberculosis
Rv2210c locus name Mycobacterium tuberculosis

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
 assay at Mycobacterium tuberculosis

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
 assay at Mycobacterium tuberculosis

Cofactor

Cofactor Comment Organism Structure
pyridoxal 5'-phosphate PLP, dependent on Mycobacterium tuberculosis

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
 additional information inhibition kinetics of L- and D-cyclserine, the inactivation follows pseudo-first-order kinetics, at least one molar equivalent of inhibitor binds to one molecule of enzyme for inactivation. Rapid inactivation by L-cycloserine with the second-order rate constant of inactivation kinact/KI_LCS of 7.32 M/s being greater than kinact/KI_DCS of 0.12 M/s Mycobacterium tuberculosis

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.088
-
 pH 8.0, 25°C, recombinant enzyme Mycobacterium tuberculosis L-Cycloserine

General Information

General Information Comment Organism
physiological function the branched-chain aminotransferase is a pyridoxal 5'-phosphate (PLP)-dependent enzyme responsible for the final step in the biosynthesis of all three branched-chain amino acids, L-leucine, L-isoleucine, and L-valine, in bacteria Mycobacterium tuberculosis