EC Number | Cloned (Comment) | Organism |
---|---|---|
3.5.1.B15 | gene pncA, DNA and amino acid sequence determination and analysis of enzyme mutants, genotyping | Mycobacterium tuberculosis |
EC Number | Protein Variants | Comment | Organism |
---|---|---|---|
3.5.1.B15 | E144K | naturally occuring mutation from PZA-resistant isolate, analysis of the resistance mechanism of the mutant strain | Mycobacterium tuberculosis |
3.5.1.B15 | L19R | naturally occuring mutation from PZA-resistant isolate | Mycobacterium tuberculosis |
3.5.1.B15 | R140H | naturally occuring mutation from PZA-resistant isolate | Mycobacterium tuberculosis |
EC Number | Metals/Ions | Comment | Organism | Structure |
---|---|---|---|---|
3.5.1.B15 | Fe2+ | required, enzyme-bound, the metal binding site contains iron (Fe2+ ion) in coordination with one aspartate (Asp49) and three histidines residues (His51, His57, and His71) | Mycobacterium tuberculosis |
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 | - |
? |
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 | - |
- |
EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | 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 | - |
? |
EC Number | Subunits | Comment | Organism |
---|---|---|---|
3.5.1.B15 | More | PZase consists of six parallel beta-sheets surrounded by alpha-helices. The metal binding site contains iron (Fe2+ ion) in coordination with one aspartate (Asp49) and three histidines residues (His51, His57, and His71), while Asp8, Lys96, and Cys138 form the catalytic triad | Mycobacterium tuberculosis |
EC Number | Synonyms | Comment | Organism |
---|---|---|---|
3.5.1.B15 | PncA | - |
Mycobacterium tuberculosis |
3.5.1.B15 | PZAse | - |
Mycobacterium tuberculosis |
EC Number | General Information | Comment | Organism |
---|---|---|---|
3.5.1.B15 | malfunction | identification and multiple analyses to unveil different mechanisms of resistance of PZase mutants L19R, R140H, and E144K, overview. The native PZase protein docking score is the maximum, showing strong binding affinity in comparison with mutants. Molecular dynamics simulations explore the effect of the variants on the biological function of PZase. Hydrogen bonding, metal ion Fe2+ deviation, and fluctuation also seem to be affected because of the mutations L19R, R140H, and E144K. The mutant variants play a significant role in PZA resistance, altering the overall activity of native PZase, including metal ion Fe2+ displacement and free energy | Mycobacterium tuberculosis |
3.5.1.B15 | additional information | residues Asp8, Lys96, and Cys138 form the catalytic triad. Receptor and ligand docking, molecular dynamics simulations, overview | Mycobacterium tuberculosis |
3.5.1.B15 | physiological function | pyrazinamide (PZA) is an important component of first-line antituberculosis drugs activated by Mycobacterium tuberculosis pyrazinamidase (PZase) into its active form pyrazinoic acid (PZA) | Mycobacterium tuberculosis |