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Literature summary extracted from

  • Junaid, M.; Khan, M.T.; Malik, S.I.; Wei, D.Q.
    Insights into the mechanisms of the pyrazinamide resistance of three pyrazinamidase mutants N11K, P69T, and D126N (2019), J. Chem. Inf. Model., 59, 498-508 .
    View publication on PubMed

Protein Variants

EC Number Protein Variants Comment Organism
3.5.1.B15 D126N site-directed mutagenesis, the mutation causes pyrazinamide resistance, the mutation is located outside of active site and has an allosteric affect Mycobacterium tuberculosis
3.5.1.B15 N11K site-directed mutagenesis, the active site mutation causes pyrazinamide resistance, destabilization of the Fe2+ binding site Mycobacterium tuberculosis
3.5.1.B15 P69T site-directed mutagenesis, the active site mutation causes pyrazinamide resistance, destabilization of the Fe2+ binding site Mycobacterium tuberculosis

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
3.5.1.B15 Fe2+ required, enzyme-bound. Mutations N11K and P69T cause destabilization of the Fe2+ binding site, structure overview 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
-
 ?

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 mechanisms of the pyrazinamide (PZA) resistance of three pyrazinamidase mutants N11K, P69T, and D126N. In general, pyrazinoic acid (PZA) resistance is caused by three genes pncA, rpsA, and panD. Among them, the pncA gene contributes 72-99% to the resistance. The binding pocket analysis shows that mutations N11K and P69T decrease the volume of the active site and hinder the correct orientation of PZA drug in the active site. Moreover, the Patchdock score is low as compared to wild-type showing the disturbance of shape complementarity between enzyme PZase and PZA drug. These mutations N11K, P69T, and D126N disturb the position of the Fe2+ ion. Among the mutations, D126N allosterically disturbs the position of the Fe2+ ion. The mutations decrease the binding affinity toward the PZA drug Mycobacterium tuberculosis