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Literature summary extracted from
- Modeling the structural origins of drug resistance to isoniazid via key mutations in Mycobacterium tuberculosis catalase-peroxidase, KatG (2018), Tuberculosis, 108, 155-162 .
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 1.11.1.21 | A110V | naturally occuring mutation in KatG which does not cause INH resistance | Mycobacterium tuberculosis |
| 1.11.1.21 | D387G | naturally occuring mutation in KatG which causes INH resistance to a very high level | Mycobacterium tuberculosis |
| 1.11.1.21 | G273C | site-directed mutagenesis near the heme center, the mutation causes a decrease in the the volume of the catalytic center | Mycobacterium tuberculosis |
| 1.11.1.21 | G316S | naturally occuring mutation in KatG which does not cause INH resistance | Mycobacterium tuberculosis |
| 1.11.1.21 | H97R/L200Q | site-directed mutagenesis near the heme center, the mutation causes a decrease in the the volume of the catalytic center | Mycobacterium tuberculosis |
| 1.11.1.21 | L499M | naturally occuring mutation in KatG which does not cause INH resistance | Mycobacterium tuberculosis |
| 1.11.1.21 | L587P | naturally occuring mutation in KatG which does not cause INH resistance | Mycobacterium tuberculosis |
| 1.11.1.21 | additional information | enzyme mutants' tertiary structures analysis, detailed overview | Mycobacterium tuberculosis |
| 1.11.1.21 | R385W | naturally occuring mutation in KatG which causes INH resistance to a very high level | Mycobacterium tuberculosis |
| 1.11.1.21 | R463L | naturally occuring mutation in KatG which does not cause INH resistance | Mycobacterium tuberculosis |
| 1.11.1.21 | S315G | site-directed mutagenesis near the heme center, the mutation causes a decrease in the the volume of the catalytic center | Mycobacterium tuberculosis |
| 1.11.1.21 | S315I | site-directed mutagenesis near the heme center, the mutation causes a decrease in the the volume of the catalytic center | Mycobacterium tuberculosis |
| 1.11.1.21 | S315N | site-directed mutagenesis near the heme center, the mutation causes a decrease in the the volume of the catalytic center | Mycobacterium tuberculosis |
| 1.11.1.21 | S315R | site-directed mutagenesis near the heme center, the mutation causes a decrease in the the volume of the catalytic center | Mycobacterium tuberculosis |
| 1.11.1.21 | S315T | naturally occuring mutation in KatG which restricts a pathway into a catalytic heme center in the active site causing INH resistance | Mycobacterium tuberculosis |
| 1.11.1.21 | S315T | site-directed mutagenesis near the heme center, the mutation causes a decrease in the the volume of the catalytic center | Mycobacterium tuberculosis |
Metals/Ions
| EC Number | Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.11.1.21 | Fe2+ | in the heme group | Mycobacterium tuberculosis |  |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.11.1.21 | 2 H2O2 | Mycobacterium tuberculosis | - |
O2 + 2 H2O | - |
? | |
| 1.11.1.21 | 2 H2O2 | Mycobacterium tuberculosis H37Rv | - |
O2 + 2 H2O | - |
? | |
| 1.11.1.21 | 2 H2O2 | Mycobacterium tuberculosis ATCC 25618 | - |
O2 + 2 H2O | - |
? | |
| 1.11.1.21 | isoniazid + H2O2 | Mycobacterium tuberculosis | pro-drug activation | ? | - |
? | |
| 1.11.1.21 | isoniazid + H2O2 | Mycobacterium tuberculosis H37Rv | pro-drug activation | ? | - |
? | |
| 1.11.1.21 | isoniazid + H2O2 | Mycobacterium tuberculosis ATCC 25618 | pro-drug activation | ? | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 1.11.1.21 | Mycobacterium tuberculosis | P9WIE5 | - |
- |
| 1.11.1.21 | Mycobacterium tuberculosis ATCC 25618 | P9WIE5 | - |
- |
| 1.11.1.21 | Mycobacterium tuberculosis H37Rv | P9WIE5 | - |
- |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.11.1.21 | 2 H2O2 | - |
Mycobacterium tuberculosis | O2 + 2 H2O | - |
? | |
| 1.11.1.21 | 2 H2O2 | - |
Mycobacterium tuberculosis H37Rv | O2 + 2 H2O | - |
? | |
| 1.11.1.21 | 2 H2O2 | - |
Mycobacterium tuberculosis ATCC 25618 | O2 + 2 H2O | - |
? | |
| 1.11.1.21 | isoniazid + H2O2 | pro-drug activation | Mycobacterium tuberculosis | ? | - |
? | |
| 1.11.1.21 | isoniazid + H2O2 | - |
Mycobacterium tuberculosis | ? | - |
? | |
| 1.11.1.21 | isoniazid + H2O2 | pro-drug activation | Mycobacterium tuberculosis H37Rv | ? | - |
? | |
| 1.11.1.21 | isoniazid + H2O2 | - |
Mycobacterium tuberculosis H37Rv | ? | - |
? | |
| 1.11.1.21 | isoniazid + H2O2 | pro-drug activation | Mycobacterium tuberculosis ATCC 25618 | ? | - |
? | |
| 1.11.1.21 | isoniazid + H2O2 | - |
Mycobacterium tuberculosis ATCC 25618 | ? | - |
? | |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 1.11.1.21 | KatG | - |
Mycobacterium tuberculosis |
| 1.11.1.21 | Rv1908c | - |
Mycobacterium tuberculosis |
Cofactor
| EC Number | Cofactor | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.11.1.21 | heme | - |
Mycobacterium tuberculosis | |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 1.11.1.21 | malfunction | resistance to INH is primarily caused by key mutations of the catalase-peroxidase, KatG, and/or promoter mutations in the inhA gene. The most frequently observed mutation involving an amino acid substitution conferring INH resistance (KatG S315T) is believed to restrict a pathway into a catalytic heme center in the active site. Effects of several mutations on the tertiary structure of KatG, focusing on conformational changes in the three channels in the protein structure, molecular dynamics study. The mutations sufficiently restrict one or more of these access channels, thus potentially preventing INH from reaching the catalytic heme, structure-based origins of INH resistance | Mycobacterium tuberculosis |
| 1.11.1.21 | additional information | enzyme structure homology modelling using the KtG structure (PDB ID 2CCA) as template, overview | Mycobacterium tuberculosis |
| 1.11.1.21 | physiological function | isoniazid (INH) is a pro-drug, that becomes activated by the endogenoous catalase-peroxidase enzyme KAtG in Mycobacterium tuberculosis. Once taken up by Mycobacterium tuberculosis, INH serves as a substrate, along with NAD+, for the KatG-catalyzed formation of nitric oxide (NO) and isonicotinyl-NAD Isonicotinyl-NAD binds to the active site of enoyl acyl carrier protein reductase, blocking fatty acid synthesis in general and the synthesis of mycolic acids, which are components of the Mycobacterium tuberculosis cell wall, in particular | Mycobacterium tuberculosis |
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