EC Number   |
General Information |
Reference |
|---|
   3.5.1.B15 | malfunction |
a nonfunctional PZase in resistant strains allows the mycobacterium to survive in the presence of pyrazinamide. Alternative or complementary mechanism of resistance may exist |
755800 |
| 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 |
-, 757448 |
| 3.5.1.B15 | more |
catalytic Cys138 |
-, 757008 |
| 3.5.1.B15 | more |
combined whole-cell high-throughput functional screening for identification of nicotinamidases/pyrazinamidases in metagenomic/polygenomic libraries, screening of mesophilic marine bacteria (MB) polygenomic library. Development of two whole-cell methods using the chemical property of one of the products formed in the enzymatic reaction (pyrazinoic or NA) to form colored complexes with stable iron salts, such as ammonium ferrous sulfate or sodium nitroprusside (SNP), optimization of the assay. A fosmid polygenomic expression library obtained from deep-sea mesophilic bacteria is screened, discovering several positive clones with the ammonium ferrous sulfate method. Quantitative rescreening with the SNP method allowing the finding of the first nicotinamidase with balanced catalytic efficiency toward nicotinamidase activity (EC 3.5.1.19) and pyrazinamide (pyrazinamidase activity) |
753679 |
| 3.5.1.B15 | more |
computational insights into pH-dependence of structure and dynamics of pyrazinamidase, comparison of wild-type and mutant enzymes, molecular dynamics simulations using the wild-type structure, PDB ID 3PL1, detailed overview. The 51-71 flap region exhibits a drastic displacement leading to enlargement of binding cavity, especially at the lower pH. Residues D8, K96, and C138 comprise an active site |
-, 757291 |
| 3.5.1.B15 | malfunction |
cumulative effect of mutations and iron substitution |
-, 756516 |
| 3.5.1.B15 | more |
development and validation of a simplified pyrazinamidase test by modifying Wayne's pyrazinamidase test for pyrazinamide drug susceptibility in Mycobacterium tuberculosis using a total of 120 complex strains/isolates, including 118 clinical isolates, and also Myycobacetrium bovis strain BCG (Tokyo substrain) and strain H37Rv, overview |
-, 757425 |
| 3.5.1.B15 | malfunction |
estimation of pyrazinamidase activity using a cell-free in vitro synthesis of pncA and its association with pyrazinamide susceptibility in Mycobacterium tuberculosis, mutant phenotypes, overview |
-, 757008 |
| 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 |
-, 757293 |
| 3.5.1.B15 | metabolism |
in Mycobacterium tuberculosis the enzyme converts the nicotinamide analogue prodrug pyrazinamide into the bacteriostatic pyrazinoic acid |
710862 |
