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Literature summary extracted from

  • Kruh, N.; Rawat, R.; Ruzsicska, B.; Tonge, P.
    Probing mechanisms of resistance to the tuberculosis drug isoniazid Conformational changes caused by inhibition of InhA, the enoyl reductase from Mycobacterium tuberculosis (2007), Protein Sci., 16, 1617-1627 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.3.1.9 expressed with N-terminal hexa-histidine motifs in Escherichia coli BL21 (DE3) pLysS cells Mycobacterium tuberculosis
1.3.1.118 expressed with N-terminal hexa-histidine motifs in Escherichia coli BL21 (DE3) pLysS cells Mycobacterium tuberculosis

Protein Variants

EC Number Protein Variants Comment Organism
1.3.1.9 I21V similar to wild-type InhA, cross-linking of the isoniazid resistant mutant gives three bands on SDS-PAGE assigned to monomer, dimer, and tetrameric forms of the protein. The inhibition of the enzyme with the isoniazid-NAD adduct results in loss of the band assigned to tetramer. In contrast, cross-linking in the presence of saturating concentrations of NADH yields a lower amount of the tetramer upon SDS-PAGE Mycobacterium tuberculosis
1.3.1.9 I47T similar to wild-type InhA, cross-linking of the isoniazid resistant mutant gives three bands on SDS-PAGE assigned to monomer, dimer, and tetrameric forms of the protein. The inhibition of the enzyme with the isoniazid-NAD adduct results in loss of the band assigned to tetramer. In contrast, cross-linking in the presence of saturating concentrations of NADH yields a lower amount of the tetramer upon SDS-PAGE Mycobacterium tuberculosis
1.3.1.9 S94A similar to wild-type InhA, cross-linking of the isoniazid resistant mutant gives three bands on SDS-PAGE assigned to monomer, dimer, and tetrameric forms of the protein. The inhibition of the enzyme with the isoniazid-NAD adduct results in loss of the band assigned to tetramer. In contrast, cross-linking in the presence of saturating concentrations of NADH yields a lower amount of the tetramer upon SDS-PAGE Mycobacterium tuberculosis
1.3.1.118 I21V similar to wild-type InhA, cross-linking of the isoniazid resistant mutant gives three bands on SDS-PAGE assigned to monomer, dimer, and tetrameric forms of the protein. The inhibition of the enzyme with the isoniazid-NAD adduct results in loss of the band assigned to tetramer. In contrast, cross-linking in the presence of saturating concentrations of NADH yields a lower amount of the tetramer upon SDS-PAGE Mycobacterium tuberculosis
1.3.1.118 I47T similar to wild-type InhA, cross-linking of the isoniazid resistant mutant gives three bands on SDS-PAGE assigned to monomer, dimer, and tetrameric forms of the protein. The inhibition of the enzyme with the isoniazid-NAD adduct results in loss of the band assigned to tetramer. In contrast, cross-linking in the presence of saturating concentrations of NADH yields a lower amount of the tetramer upon SDS-PAGE Mycobacterium tuberculosis
1.3.1.118 S94A similar to wild-type InhA, cross-linking of the isoniazid resistant mutant gives three bands on SDS-PAGE assigned to monomer, dimer, and tetrameric forms of the protein. The inhibition of the enzyme with the isoniazid-NAD adduct results in loss of the band assigned to tetramer. In contrast, cross-linking in the presence of saturating concentrations of NADH yields a lower amount of the tetramer upon SDS-PAGE Mycobacterium tuberculosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.3.1.9 isoniazid inhibits InhA via formation of a covalent adduct with NAD+. KatG, the mycobacterial catalase-peroxidase, is essential for isoniazid activation. While cross-linking studies indicate that enzyme inhibition causes dissociation of the InhA tetramer into dimers, analytical ultracentrifugation and size exclusion chromatography reveal that ligand binding causes a conformational change in the protein that prevents cross-linking across one of the dimer-dimer interfaces in the InhA tetramer Mycobacterium tuberculosis
1.3.1.118 isoniazid inhibits InhA via formation of a covalent adduct with NAD+. KatG, the mycobacterial catalase-peroxidase, is essential for isoniazid activation. While cross-linking studies indicate that enzyme inhibition causes dissociation of the InhA tetramer into dimers, analytical ultracentrifugation and size exclusion chromatography reveal that ligand binding causes a conformational change in the protein that prevents cross-linking across one of the dimer-dimer interfaces in the InhA tetramer Mycobacterium tuberculosis

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
1.3.1.9 114600
-
 gel filtration Mycobacterium tuberculosis
1.3.1.118 114600
-
 gel filtration Mycobacterium tuberculosis

Organism

EC Number Organism UniProt Comment Textmining
1.3.1.9 Mycobacterium tuberculosis P9WGR1
-
-
1.3.1.9 Mycobacterium tuberculosis ATCC 25618 P9WGR1
-
-
1.3.1.118 Mycobacterium tuberculosis P9WGR1
-
-
1.3.1.118 Mycobacterium tuberculosis ATCC 25618 P9WGR1
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.3.1.9
-
 Mycobacterium tuberculosis
1.3.1.118
-
 Mycobacterium tuberculosis

Subunits

EC Number Subunits Comment Organism
1.3.1.9 tetramer
-
 Mycobacterium tuberculosis
1.3.1.118 tetramer
-
 Mycobacterium tuberculosis

Synonyms

EC Number Synonyms Comment Organism
1.3.1.9 FAS-II enoyl reductase
-
 Mycobacterium tuberculosis
1.3.1.9 InhA
-
 Mycobacterium tuberculosis
1.3.1.118 FAS-II enoyl reductase
-
 Mycobacterium tuberculosis
1.3.1.118 InhA
-
 Mycobacterium tuberculosis

Cofactor

EC Number Cofactor Comment Organism Structure
1.3.1.9 NADH while NADH binding to wild-type InhA is hyperbolic, the InhA mutants bind the cofactor with positive cooperativity, suggesting that the mutations permit access to a second conformational state of the protein Mycobacterium tuberculosis
1.3.1.118 NADH while NADH binding to wild-type InhA is hyperbolic, the InhA mutants bind the cofactor with positive cooperativity, suggesting that the mutations permit access to a second conformational state of the protein Mycobacterium tuberculosis