BRENDA - Enzyme Database show

A multi-scale computational study on the mechanism of Streptococcus pneumoniae nicotinamidase (SpNic)

Ion, B.F.; Kazim, E.; Gauld, J.W.; Molecules 19, 15735-15753 (2014)

Data extracted from this reference:

Application
EC Number
Application
Commentary
Organism
3.5.1.19
drug development
while nicotinamidases are widespread in nature they are not occuring within mammals and present a potential drug target. The enzymes can be used in the activation of tuberculosis prodrugs such as pyrazinamide
Streptococcus pneumoniae
Metals/Ions
EC Number
Metals/Ions
Commentary
Organism
Structure
3.5.1.19
Zn2+
zinc-dependent enzyme
Streptococcus pneumoniae
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
3.5.1.19
nicotinamide + H2O
Streptococcus pneumoniae
-
nicotinate + NH3
-
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
3.5.1.19
Streptococcus pneumoniae
-
-
-
Reaction
EC Number
Reaction
Commentary
Organism
3.5.1.19
nicotinamide + H2O = nicotinate + NH3
catalytic mechanism in two stages: (i) formation of a tetrahedral thioester enzyme-substrate intermediate (with the sulfur of Cys136 nucleophilically attacks the nicotinamidase substrate's carbonyl carbon while concomitantly the Cys136-SH thiol proton is transferred onto the substrate's amide group nitrogen) and (ii) hydrolysis of the thioester bond to give the products, overview. The catalytic triad comprises Lys103, Asp9, and Cys136, substrate binding and roles of active site residues of the enzyme from Streptococcus pneumoniae. The active site Lys103 likely plays a role in stabilizing the thiolate of Cys136 during the reaction
Streptococcus pneumoniae
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
3.5.1.19
nicotinamide + H2O
-
734741
Streptococcus pneumoniae
nicotinate + NH3
-
-
-
?
3.5.1.19
pyrazinamide + H2O
-
734741
Streptococcus pneumoniae
pyrazinoic acid + NH3
-
-
-
?
Application (protein specific)
EC Number
Application
Commentary
Organism
3.5.1.19
drug development
while nicotinamidases are widespread in nature they are not occuring within mammals and present a potential drug target. The enzymes can be used in the activation of tuberculosis prodrugs such as pyrazinamide
Streptococcus pneumoniae
Metals/Ions (protein specific)
EC Number
Metals/Ions
Commentary
Organism
Structure
3.5.1.19
Zn2+
zinc-dependent enzyme
Streptococcus pneumoniae
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
3.5.1.19
nicotinamide + H2O
Streptococcus pneumoniae
-
nicotinate + NH3
-
-
?
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
3.5.1.19
nicotinamide + H2O
-
734741
Streptococcus pneumoniae
nicotinate + NH3
-
-
-
?
3.5.1.19
pyrazinamide + H2O
-
734741
Streptococcus pneumoniae
pyrazinoic acid + NH3
-
-
-
?
General Information
EC Number
General Information
Commentary
Organism
3.5.1.19
evolution
nicotinamidases are a family of peptide hydrolases that generally contain a Zn2+ ion
Streptococcus pneumoniae
3.5.1.19
metabolism
nicotinamidase is a key enzyme in NAD+ metabolism
Streptococcus pneumoniae
3.5.1.19
additional information
catalytic mechanism, substrate binding and roles of active site residues, quantum mechanics/molecular mechanics methods and modeling, overview. The polar protein environment has a significant effect in stabilizing reaction intermediates and in particular transition states
Streptococcus pneumoniae
General Information (protein specific)
EC Number
General Information
Commentary
Organism
3.5.1.19
evolution
nicotinamidases are a family of peptide hydrolases that generally contain a Zn2+ ion
Streptococcus pneumoniae
3.5.1.19
metabolism
nicotinamidase is a key enzyme in NAD+ metabolism
Streptococcus pneumoniae
3.5.1.19
additional information
catalytic mechanism, substrate binding and roles of active site residues, quantum mechanics/molecular mechanics methods and modeling, overview. The polar protein environment has a significant effect in stabilizing reaction intermediates and in particular transition states
Streptococcus pneumoniae