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Literature summary extracted from
- Structural and quantum mechanical computations to elucidate the altered binding mechanism of metal and drug with pyrazinamidase from Mycobacterium tuberculosis due to mutagenicity (2018), J. Mol. Graph. Model., 80, 126-131 .
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 3.5.1.B15 | C138Y | site-directed mutagenesis | Mycobacterium tuberculosis |
| 3.5.1.B15 | D12A | site-directed mutagenesis | Mycobacterium tuberculosis |
| 3.5.1.B15 | D12G | site-directed mutagenesis | Mycobacterium tuberculosis |
| 3.5.1.B15 | D49N | site-directed mutagenesis | Mycobacterium tuberculosis |
| 3.5.1.B15 | F94L | site-directed mutagenesis | Mycobacterium tuberculosis |
| 3.5.1.B15 | G24D | site-directed mutagenesis | Mycobacterium tuberculosis |
| 3.5.1.B15 | G78C | site-directed mutagenesis | Mycobacterium tuberculosis |
| 3.5.1.B15 | H51Q | site-directed mutagenesis | Mycobacterium tuberculosis |
| 3.5.1.B15 | H57D | site-directed mutagenesis | Mycobacterium tuberculosis |
| 3.5.1.B15 | L116P | site-directed mutagenesis | Mycobacterium tuberculosis |
| 3.5.1.B15 | S67P | site-directed mutagenesis | Mycobacterium tuberculosis |
| 3.5.1.B15 | T135P | site-directed mutagenesis | Mycobacterium tuberculosis |
Metals/Ions
| EC Number | Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|---|
| 3.5.1.B15 | Fe2+ | iron shows weak binding with the metal coordination site of the mutant proteins due to alteration in electron transfer mechanism | Mycobacterium tuberculosis |  |
| 3.5.1.B15 | additional information | Asp49, His51, His57, and His71 are the metal ion binding residues | Mycobacterium tuberculosis |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 3.5.1.B15 | pyrazinamide + H2O | Mycobacterium tuberculosis | - |
pyrazinoic acid + NH3 | - |
? | |
| 3.5.1.B15 | pyrazinamide + H2O | Mycobacterium tuberculosis H37Rv | - |
pyrazinoic acid + NH3 | - |
? | |
| 3.5.1.B15 | pyrazinamide + H2O | Mycobacterium tuberculosis ATCC 25618 | - |
pyrazinoic acid + NH3 | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 3.5.1.B15 | Mycobacterium tuberculosis | I6XD65 | - |
- |
| 3.5.1.B15 | Mycobacterium tuberculosis ATCC 25618 | I6XD65 | - |
- |
| 3.5.1.B15 | Mycobacterium tuberculosis H37Rv | I6XD65 | - |
- |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 3.5.1.B15 | additional information | docking study of PZA in the binding pocket of PZase | Mycobacterium tuberculosis | ? | - |
- |
|
| 3.5.1.B15 | additional information | docking study of PZA in the binding pocket of PZase | Mycobacterium tuberculosis H37Rv | ? | - |
- |
|
| 3.5.1.B15 | additional information | docking study of PZA in the binding pocket of PZase | Mycobacterium tuberculosis ATCC 25618 | ? | - |
- |
|
| 3.5.1.B15 | pyrazinamide + H2O | - |
Mycobacterium tuberculosis | pyrazinoic acid + NH3 | - |
? | |
| 3.5.1.B15 | pyrazinamide + H2O | - |
Mycobacterium tuberculosis H37Rv | pyrazinoic acid + NH3 | - |
? | |
| 3.5.1.B15 | pyrazinamide + H2O | - |
Mycobacterium tuberculosis ATCC 25618 | pyrazinoic acid + NH3 | - |
? | |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 3.5.1.B15 | PncA | - |
Mycobacterium tuberculosis |
| 3.5.1.B15 | PZAse | - |
Mycobacterium tuberculosis |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 3.5.1.B15 | malfunction | analysis of mutations in pyrazinamidase and effects of the mutations at the metal coordination site and conformational changes in PZase binding cavity on the enzyme activity, quantum mechanical calculations, overview. Iron shows weak binding with the metal coordination site of the mutant proteins due to alteration in electron transfer mechanism. The binding cavity of the mutant PZase has undergone major conformational changes as the volume of pocket increased due to bulky R-chains of mutated amino acids. These conformational changes lead to weak binding of the drug at binding cavity of PZase and reduce the drug activation mechanism leading to increased drug resistance in the bacterial strains. The template structure used is the tertiary structure of pyrazinamidase from Mycobacterium tuberculosis, PDB ID 3PL1 | Mycobacterium tuberculosis |
| 3.5.1.B15 | additional information | structural and quantum mechanical computations to elucidate the altered binding mechanism of metal and drug with Mycobacterium tuberculosis pyrazinamidase due to mutagenicity. Residues Asp8, Lys96, and Cys138 play a pivotal role in catalysis | Mycobacterium tuberculosis |
| 3.5.1.B15 | physiological function | pyrazinamidase, activator for pyrazinamide, leads to resistance against the drug pyrazinamide due to mutagenicity across the world | Mycobacterium tuberculosis |
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