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Literature summary extracted from

  • Khan, M.; Junaid, M.; Mao, X.; Wang, Y.; Hussain, A.; Malik, S.; Wei, D.
    Pyrazinamide resistance and mutations L19R, R140H, and E144K in pyrazinamidase of Mycobacterium tuberculosis (2019), J. Cell. Biochem., 120, 7154-7166 .
    View publication on PubMed

Cloned(Commentary)

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

Protein Variants

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

Metals/Ions

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

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 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
-
?

Subunits

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

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 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