BRENDA - Enzyme Database show

Specificity and mechanism of Acinetobacter baumanii nicotinamidase: Implications for activation of the front-line tuberculosis drug pyrazinamide

Fyfe, P.; Rao, V.; Zemla, A.; Cameron, S.; Hunter, W.; Angew. Chem. Int. Ed. Engl. 48, 9176-9179 (2009)

Data extracted from this reference:

Metals/Ions
EC Number
Metals/Ions
Commentary
Organism
Structure
3.5.1.B15
Fe2+
activates
Acinetobacter baumannii
3.5.1.B15
Mn2+
activates
Acinetobacter baumannii
3.5.1.B15
additional information
PncA is a divalent cation-dependent enzyme
Acinetobacter baumannii
3.5.1.B15
Zn2+
activates, best cation, the active site Cys159 is located at the N-terminus of a6 at one side of the active site with the Zn2+ ion positioned on the other side. The metal ion is bound tightly in the AbPncA active site
Acinetobacter baumannii
3.5.1.19
Fe2+
activates
Acinetobacter baumannii
3.5.1.19
Mn2+
activates
Acinetobacter baumannii
3.5.1.19
additional information
PncA is a divalent cation-dependent enzyme
Acinetobacter baumannii
3.5.1.19
Zn2+
activates, best cation, the active site Cys159 is located at the N-terminus of a6 at one side of the active site with the Zn2+ ion positioned on the other side. The metal ion is bound tightly in the AbPncA active site
Acinetobacter baumannii
Molecular Weight [Da]
EC Number
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
3.5.1.B15
47000
-
gel filtratrion and analytical ultracentrifugation
Acinetobacter baumannii
3.5.1.19
47000
-
gel filtratrion and analytical ultracentrifugation
Acinetobacter baumannii
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
3.5.1.B15
pyrazinamide + H2O
Acinetobacter baumannii
a nicotinamide prodrug. In Mycobacterium tuberculosis the enzyme converts the nicotinamide analogue prodrug pyrazinamide into the bacteriostatic pyrazinoic acid
pyrazinoic acid + NH3
a bacteriostatic drug
-
?
3.5.1.19
nicotinamide + H2O
Acinetobacter baumannii
-
nicotinate + NH3
-
-
?
3.5.1.19
pyrazinamide + H2O
Acinetobacter baumannii
a nicotinamide prodrug. In Mycobacterium tuberculosis the enzyme converts the nicotinamide analogue prodrug pyrazinamide into the bacteriostatic pyrazinoic acid, hence the alternative name, pyrazinamidase, PncA
pyrazinoic acid + NH3
a bacteriostatic drug
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
3.5.1.B15
Acinetobacter baumannii
-
-
-
3.5.1.19
Acinetobacter baumannii
-
-
-
Reaction
EC Number
Reaction
Commentary
Organism
3.5.1.19
nicotinamide + H2O = nicotinate + NH3
the active site Cys159, conserved and essential, is located at the N-terminus of a6 at one side of the active site with the Zn2+ ion positioned on the other side. The metal ion is bound tightly in the AbPncA active site. The reaction proceeds in a four-stage mechanism via a tetrahedral and an acyl intermediate, overview
Acinetobacter baumannii
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
3.5.1.B15
pyrazinamide + H2O
a nicotinamide prodrug. In Mycobacterium tuberculosis the enzyme converts the nicotinamide analogue prodrug pyrazinamide into the bacteriostatic pyrazinoic acid
710862
Acinetobacter baumannii
pyrazinoic acid + NH3
a bacteriostatic drug
-
-
?
3.5.1.19
nicotinamide + H2O
-
710862
Acinetobacter baumannii
nicotinate + NH3
-
-
-
?
3.5.1.19
nicotinamide + H2O
active site structure, overview
710862
Acinetobacter baumannii
nicotinate + NH3
-
-
-
?
3.5.1.19
pyrazinamide + H2O
a nicotinamide prodrug. In Mycobacterium tuberculosis the enzyme converts the nicotinamide analogue prodrug pyrazinamide into the bacteriostatic pyrazinoic acid, hence the alternative name, pyrazinamidase, PncA
710862
Acinetobacter baumannii
pyrazinoic acid + NH3
a bacteriostatic drug
-
-
?
Subunits
EC Number
Subunits
Commentary
Organism
3.5.1.B15
dimer
-
Acinetobacter baumannii
3.5.1.19
dimer
-
Acinetobacter baumannii
Metals/Ions (protein specific)
EC Number
Metals/Ions
Commentary
Organism
Structure
3.5.1.B15
Fe2+
activates
Acinetobacter baumannii
3.5.1.B15
Mn2+
activates
Acinetobacter baumannii
3.5.1.B15
additional information
PncA is a divalent cation-dependent enzyme
Acinetobacter baumannii
3.5.1.B15
Zn2+
activates, best cation, the active site Cys159 is located at the N-terminus of a6 at one side of the active site with the Zn2+ ion positioned on the other side. The metal ion is bound tightly in the AbPncA active site
Acinetobacter baumannii
3.5.1.19
Fe2+
activates
Acinetobacter baumannii
3.5.1.19
Mn2+
activates
Acinetobacter baumannii
3.5.1.19
additional information
PncA is a divalent cation-dependent enzyme
Acinetobacter baumannii
3.5.1.19
Zn2+
activates, best cation, the active site Cys159 is located at the N-terminus of a6 at one side of the active site with the Zn2+ ion positioned on the other side. The metal ion is bound tightly in the AbPncA active site
Acinetobacter baumannii
Molecular Weight [Da] (protein specific)
EC Number
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
3.5.1.B15
47000
-
gel filtratrion and analytical ultracentrifugation
Acinetobacter baumannii
3.5.1.19
47000
-
gel filtratrion and analytical ultracentrifugation
Acinetobacter baumannii
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
3.5.1.B15
pyrazinamide + H2O
Acinetobacter baumannii
a nicotinamide prodrug. In Mycobacterium tuberculosis the enzyme converts the nicotinamide analogue prodrug pyrazinamide into the bacteriostatic pyrazinoic acid
pyrazinoic acid + NH3
a bacteriostatic drug
-
?
3.5.1.19
nicotinamide + H2O
Acinetobacter baumannii
-
nicotinate + NH3
-
-
?
3.5.1.19
pyrazinamide + H2O
Acinetobacter baumannii
a nicotinamide prodrug. In Mycobacterium tuberculosis the enzyme converts the nicotinamide analogue prodrug pyrazinamide into the bacteriostatic pyrazinoic acid, hence the alternative name, pyrazinamidase, PncA
pyrazinoic acid + NH3
a bacteriostatic drug
-
?
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
3.5.1.B15
pyrazinamide + H2O
a nicotinamide prodrug. In Mycobacterium tuberculosis the enzyme converts the nicotinamide analogue prodrug pyrazinamide into the bacteriostatic pyrazinoic acid
710862
Acinetobacter baumannii
pyrazinoic acid + NH3
a bacteriostatic drug
-
-
?
3.5.1.19
nicotinamide + H2O
-
710862
Acinetobacter baumannii
nicotinate + NH3
-
-
-
?
3.5.1.19
nicotinamide + H2O
active site structure, overview
710862
Acinetobacter baumannii
nicotinate + NH3
-
-
-
?
3.5.1.19
pyrazinamide + H2O
a nicotinamide prodrug. In Mycobacterium tuberculosis the enzyme converts the nicotinamide analogue prodrug pyrazinamide into the bacteriostatic pyrazinoic acid, hence the alternative name, pyrazinamidase, PncA
710862
Acinetobacter baumannii
pyrazinoic acid + NH3
a bacteriostatic drug
-
-
?
Subunits (protein specific)
EC Number
Subunits
Commentary
Organism
3.5.1.B15
dimer
-
Acinetobacter baumannii
3.5.1.19
dimer
-
Acinetobacter baumannii
General Information
EC Number
General Information
Commentary
Organism
3.5.1.B15
metabolism
in Mycobacterium tuberculosis the enzyme converts the nicotinamide analogue prodrug pyrazinamide into the bacteriostatic pyrazinoic acid
Acinetobacter baumannii
3.5.1.B15
physiological function
the reaction product pyrazinoic acid inhibits Mycobacterium tuberculosis type I fatty acid synthase, represses mycolic acid biosynthesis, and appears to affect membrane energetics and acidification of the cytoplasm
Acinetobacter baumannii
3.5.1.19
metabolism
the enzyme catalyzes the deamination of nicotinamide, which is an important step in the NAD+ salvage pathway. In Mycobacterium tuberculosis the enzyme converts the nicotinamide analogue prodrug pyrazinamide into the bacteriostatic pyrazinoic acid, hence the alternative name, pyrazinamidase, PncA
Acinetobacter baumannii
3.5.1.19
physiological function
the reaction product pyrazinoic acid inhibits Mycobacterium tuberculosis type I fatty acid synthase, represses mycolic acid biosynthesis, and appears to affect membrane energetics and acidification of the cytoplasm
Acinetobacter baumannii
General Information (protein specific)
EC Number
General Information
Commentary
Organism
3.5.1.B15
metabolism
in Mycobacterium tuberculosis the enzyme converts the nicotinamide analogue prodrug pyrazinamide into the bacteriostatic pyrazinoic acid
Acinetobacter baumannii
3.5.1.B15
physiological function
the reaction product pyrazinoic acid inhibits Mycobacterium tuberculosis type I fatty acid synthase, represses mycolic acid biosynthesis, and appears to affect membrane energetics and acidification of the cytoplasm
Acinetobacter baumannii
3.5.1.19
metabolism
the enzyme catalyzes the deamination of nicotinamide, which is an important step in the NAD+ salvage pathway. In Mycobacterium tuberculosis the enzyme converts the nicotinamide analogue prodrug pyrazinamide into the bacteriostatic pyrazinoic acid, hence the alternative name, pyrazinamidase, PncA
Acinetobacter baumannii
3.5.1.19
physiological function
the reaction product pyrazinoic acid inhibits Mycobacterium tuberculosis type I fatty acid synthase, represses mycolic acid biosynthesis, and appears to affect membrane energetics and acidification of the cytoplasm
Acinetobacter baumannii