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Literature summary for 3.5.1.B15 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
Search for more literature for 3.5.1.B15

Cloned(Commentary)

Cloned (Comment) Organism
gene pncA, DNA and amino acid sequence determination and analysis of enzyme mutants, genotyping Mycobacterium tuberculosis

Protein Variants

Protein Variants Comment Organism
E144K naturally occuring mutation from PZA-resistant isolate, analysis of the resistance mechanism of the mutant strain Mycobacterium tuberculosis
L19R naturally occuring mutation from PZA-resistant isolate Mycobacterium tuberculosis
R140H naturally occuring mutation from PZA-resistant isolate Mycobacterium tuberculosis

Metals/Ions

Metals/Ions Comment Organism Structure
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)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
pyrazinamide + H2O Mycobacterium tuberculosis
-
 pyrazinoic acid + NH3
-
 ?
pyrazinamide + H2O Mycobacterium tuberculosis H37Rv
-
 pyrazinoic acid + NH3
-
 ?
pyrazinamide + H2O Mycobacterium tuberculosis ATCC 25618
-
 pyrazinoic acid + NH3
-
 ?

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis I6XD65
-
-
Mycobacterium tuberculosis ATCC 25618 I6XD65
-
-
Mycobacterium tuberculosis H37Rv I6XD65
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
pyrazinamide + H2O
-
 Mycobacterium tuberculosis pyrazinoic acid + NH3
-
 ?
pyrazinamide + H2O
-
 Mycobacterium tuberculosis H37Rv pyrazinoic acid + NH3
-
 ?
pyrazinamide + H2O
-
 Mycobacterium tuberculosis ATCC 25618 pyrazinoic acid + NH3
-
 ?

Subunits

Subunits Comment Organism
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

Synonyms Comment Organism
PncA
-
 Mycobacterium tuberculosis
PZAse
-
 Mycobacterium tuberculosis

General Information

General Information Comment Organism
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
additional information residues Asp8, Lys96, and Cys138 form the catalytic triad. Receptor and ligand docking, molecular dynamics simulations, overview Mycobacterium tuberculosis
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