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Literature summary for 1.11.1.21 extracted from

  • Purkan, P.; Ihsanawati, I.; Natalia, D.; Syah, Y.; Retnoningrum, D.; Siswanto, I.
    Molecular analysis of katG encoding catalase-peroxidase from clinical isolate of isoniazid-resistant Mycobacterium tuberculosis (2018), J. Med. Life, 11, 160-167 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.11.1.21

Cloned(Commentary)

Cloned (Comment) Organism
gene katG, recombinant expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3), subcloning in Escherichia coli strain DH5alpha Mycobacterium tuberculosis

Protein Variants

Protein Variants Comment Organism
G421S site-directed mutagenesis, of amino acids alteration in the mutant, substitution of T354I and G421S create significant instability in the adduct triad complex (Trp107-Tyr229-Met255), a part of the active site of the catalase-peroxidase enzyme in the model structure analysis Mycobacterium tuberculosis
additional information dynamic simulations of enzyme mutants bound to isoniazid (INH) Mycobacterium tuberculosis
S140N/A350T/R463L/R463G/L587M the mutant katG has catalase-peroxidase activities higher than wild-type katG and exhibits INH sensitivity Mycobacterium tuberculosis
S315T naturally occuring mutant, the mutant katG retains peroxidase and catalase activity as 60% and 40%, respectively, from wild-type activity, the mutant develops INH inhibitory levels to the transformant BCG corresponding to the decline of its protein activity Mycobacterium tuberculosis
T354I site-directed mutagenesis, of amino acids alteration in the mutant, substitution of T354I and G421S create significant instability in the adduct triad complex (Trp107-Tyr229-Met255), a part of the active site of the catalase-peroxidase enzyme in the model structure analysis Mycobacterium tuberculosis
T354I/G421S/R463L/V721M naturally occuring mutation. The Mycobacterium tubeculsosis clinical isolate R2 contains four mutations, i.e. C1061T, G1261A, G1388T, G2161A, which correspond to the amino acid substitutions T354I, G421S, R463L, and V721M, respectively, leading to high level isoniazid (INH) resistance. The mutant enzyme showed 86.5% of catalase and 45% of peroxidase activities in comparison to the wild-type enzyme. Substitutions of T354I and G421S in mutant katG R2 create significant instability in the adduct triad complex (Trp107-Tyr229-Met255), a part of the active site of the catalase-peroxidase enzyme in the model structure analysis. Mutant phenotype and stability, overview Mycobacterium tuberculosis

Metals/Ions

Metals/Ions Comment Organism Structure
Fe2+ the heme group Mycobacterium tuberculosis

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
160000
-
 about Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2 H2O2 Mycobacterium tuberculosis
-
 O2 + 2 H2O
-
 ?
2 H2O2 Mycobacterium tuberculosis H37Rv
-
 O2 + 2 H2O
-
 ?
2 H2O2 Mycobacterium tuberculosis ATCC 25618
-
 O2 + 2 H2O
-
 ?
isoniazid + H2O2 Mycobacterium tuberculosis
-
 ?
-
 ?
isoniazid + H2O2 Mycobacterium tuberculosis H37Rv
-
 ?
-
 ?
isoniazid + H2O2 Mycobacterium tuberculosis ATCC 25618
-
 ?
-
 ?
o-dianisidine + H2O2 Mycobacterium tuberculosis
-
 oxidized o-dianisidine + 2 H2O
-
 ?
o-dianisidine + H2O2 Mycobacterium tuberculosis H37Rv
-
 oxidized o-dianisidine + 2 H2O
-
 ?
o-dianisidine + H2O2 Mycobacterium tuberculosis ATCC 25618
-
 oxidized o-dianisidine + 2 H2O
-
 ?

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WIE5
-
-
Mycobacterium tuberculosis ATCC 25618 P9WIE5
-
-
Mycobacterium tuberculosis H37Rv P9WIE5
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2 H2O2
-
 Mycobacterium tuberculosis O2 + 2 H2O
-
 ?
2 H2O2 peroxidase activity Mycobacterium tuberculosis O2 + 2 H2O
-
 ?
2 H2O2
-
 Mycobacterium tuberculosis H37Rv O2 + 2 H2O
-
 ?
2 H2O2 peroxidase activity Mycobacterium tuberculosis H37Rv O2 + 2 H2O
-
 ?
2 H2O2
-
 Mycobacterium tuberculosis ATCC 25618 O2 + 2 H2O
-
 ?
2 H2O2 peroxidase activity Mycobacterium tuberculosis ATCC 25618 O2 + 2 H2O
-
 ?
isoniazid + H2O2
-
 Mycobacterium tuberculosis ?
-
 ?
isoniazid + H2O2
-
 Mycobacterium tuberculosis H37Rv ?
-
 ?
isoniazid + H2O2
-
 Mycobacterium tuberculosis ATCC 25618 ?
-
 ?
o-dianisidine + H2O2
-
 Mycobacterium tuberculosis oxidized o-dianisidine + 2 H2O
-
 ?
o-dianisidine + H2O2 catalase activity Mycobacterium tuberculosis oxidized o-dianisidine + 2 H2O
-
 ?
o-dianisidine + H2O2
-
 Mycobacterium tuberculosis H37Rv oxidized o-dianisidine + 2 H2O
-
 ?
o-dianisidine + H2O2 catalase activity Mycobacterium tuberculosis H37Rv oxidized o-dianisidine + 2 H2O
-
 ?
o-dianisidine + H2O2
-
 Mycobacterium tuberculosis ATCC 25618 oxidized o-dianisidine + 2 H2O
-
 ?
o-dianisidine + H2O2 catalase activity Mycobacterium tuberculosis ATCC 25618 oxidized o-dianisidine + 2 H2O
-
 ?

Subunits

Subunits Comment Organism
homodimer 2 * 80000, about SDS-PAGE Mycobacterium tuberculosis
More each subunit has two dominant alpha-helix domains, which means that the domains originated from gene duplication. The N domain has a heme, an active site and a substrate binding site. While the C domain does not have those, its presence is needed to support the overall enzyme activity. The catalytic activity of katG is mediated by some residues in the active site that resided around the heme group Mycobacterium tuberculosis

Synonyms

Synonyms Comment Organism
KatG
-
 Mycobacterium tuberculosis

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
22
-
 assay at room temperature Mycobacterium tuberculosis

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
4.5
-
 peroxidase activity, assay at Mycobacterium tuberculosis
7
-
 catalase activity, assay at Mycobacterium tuberculosis

Cofactor

Cofactor Comment Organism Structure
heme
-
 Mycobacterium tuberculosis

General Information

General Information Comment Organism
malfunction mutations of the katG gene in Mycobacterium tuberculosis (T354I, G421S, R463L, and V721M) are a major INH resistance mechanism. The Mycobacterium tuberculosis clinical isolate R2 shows INH resistance at a high level of 0.01 mg/ml Mycobacterium tuberculosis
metabolism to function as an antitubercular agent, INH requires activation of enzyme catalase-peroxidase encoded by Mycobacterium tuberculosis gene katG. The INH is bound by catalase-peroxidase in its active site, then converted to an isonicotinoyl acyl radical through the use of a diazene intermediate. The isonicotinoyl acyl radical interacts with the NADH electron donor in the active site of the enoyl ACP reductase (InhA) enzyme. The NAD-INH complex is known as a potent inhibitor of InhA, the enzyme that has an important role in the biosynthesis of mycolic acid, the cell wall component in mycobacteria Mycobacterium tuberculosis
additional information each subunit has two dominant alpha-helix domains, which means that the domains originated from gene duplication. The N domain has a heme, an active site and a substrate binding site. While the C domain does not have those, its presence is needed to support the overall enzyme activity. The catalytic activity of katG is mediated by some residues in the active site that resided around the heme group. The heme is surrounded by six residues which are Arg104, Trp107 and His108 in the distal pocket, and His270, Trp321 and Asp381 in the proximal pocket. In the heme, the Trp107 residue is connected to Tyr229 and Met255 residues to form an adduct triad complex. The adduct triad is likely conserved in many catalase-peroxidase structures and it is involved in the catalase activity [9]. The binding of INH to katG takes place at the edges of the ?-meso heme. In the region, the residues of the distal pocket, i.e., Arg104, Trp107 and His108, are involved in the interactions with INH. The adduct triad complex (Trp107-Tyr229-Met255) is a part of the active site of the catalase-peroxidase enzyme Mycobacterium tuberculosis
physiological function isoniazid (INH) is a drug for the treatment of tuberculosis in patients infected with Mycobacterium tuberculosis. The katG enzyme, a catalase-peroxidase, encoded by gene katG in Mycobacterium tuberculosis activates the pro-drug INH Mycobacterium tuberculosis