UniProt functional annotation for P9WIL5



	UniProt functional annotation for P9WIL5

UniProt code: P9WIL5.

Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).

Taxonomy: Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae; Mycobacterium; Mycobacterium tuberculosis complex.

Function: Catalyzes the condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate. {ECO:0000269|PubMed:11669627}.

Catalytic activity: Reaction=(R)-pantoate + ATP + beta-alanine = (R)-pantothenate + AMP + diphosphate + H(+); Xref=Rhea:RHEA:10912, ChEBI:CHEBI:15378, ChEBI:CHEBI:15980, ChEBI:CHEBI:29032, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57966, ChEBI:CHEBI:456215; EC=6.3.2.1; Evidence={ECO:0000269|PubMed:12717031};

Activity regulation: Pantothenate exhibits uncompetitive inhibition toward both D-pantoate and ATP, and non-competitive inhibition toward beta-alanine. AMPCPP exhibits competitive inhibition toward ATP, uncompetitive inhibition toward beta-alanine, and non-competitive inhibition toward D-pantoate. The enzyme is most active in the presence of magnesium or manganese. Other divalent cations (cobalt, nickel, zinc) are less effective. {ECO:0000269|PubMed:11669627}.

Biophysicochemical properties: Kinetic parameters: KM=130 uM for D-pantoate {ECO:0000269|PubMed:11669627, ECO:0000269|PubMed:15170354}; KM=800 uM for beta-alanine {ECO:0000269|PubMed:11669627, ECO:0000269|PubMed:15170354}; KM=2600 uM for ATP {ECO:0000269|PubMed:11669627, ECO:0000269|PubMed:15170354}; KM=25.4 mM for 2-mercaptoethylamine {ECO:0000269|PubMed:11669627, ECO:0000269|PubMed:15170354}; KM=36 mM for carbamate {ECO:0000269|PubMed:11669627, ECO:0000269|PubMed:15170354}; KM=72 mM for 5-aminovalerate {ECO:0000269|PubMed:11669627, ECO:0000269|PubMed:15170354}; KM=79 mM for methylamine {ECO:0000269|PubMed:11669627, ECO:0000269|PubMed:15170354}; KM=84 mM for glycine {ECO:0000269|PubMed:11669627, ECO:0000269|PubMed:15170354}; KM=93 mM for ethylamine {ECO:0000269|PubMed:11669627, ECO:0000269|PubMed:15170354}; KM=103 mM for taurine {ECO:0000269|PubMed:11669627, ECO:0000269|PubMed:15170354}; KM=108 mM for glycolate {ECO:0000269|PubMed:11669627, ECO:0000269|PubMed:15170354}; KM=335 mM for gamma-aminobutyrate {ECO:0000269|PubMed:11669627, ECO:0000269|PubMed:15170354}; KM=580 mM for gamma-amino-beta-hydroxybutyrate {ECO:0000269|PubMed:11669627, ECO:0000269|PubMed:15170354};

Pathway: Cofactor biosynthesis; (R)-pantothenate biosynthesis; (R)- pantothenate from (R)-pantoate and beta-alanine: step 1/1.

Subcellular location: Cytoplasm {ECO:0000305}.

Mass spectrometry: Mass=32545; Method=Electrospray; Evidence={ECO:0000269|PubMed:11669627};

Disruption phenotype: Simultaneous disruption of panD and panC gives a mutant unable to grow in the absence of panothenate. The double mutant has a highly attenuated disease response in BALB/c and SCID mice; immunocompromised BALB/c SCID mice survive on average 36 weeks as opposed to 5 weeks for mice infected with wild-type bacteria, while immunocompetent BALB/c mice survive indefinitely. In wild-type mice bacteria grow for 3 weeks then undergo a steady decline, bacteria persist over 8 months in SCID mice (PubMed:12219086). The double mutant is sensitive to PZA but not POA in liquid culture, beta-alanine but not pantothenate antagonize the effect of PZA at pH 5.8 (PubMed:25246400). {ECO:0000269|PubMed:12219086, ECO:0000269|PubMed:25246400}.

Biotechnology: Subcutaneous immunization with the double panD and panC bacterial disruption mutant protects mice for over a year against subsequent virulent M.tuberculosis (strain Erdman) infections; mice show mild lung inflammation and fibrosis despite a chronic bacterila infection. This is a promising attenuated vaccine strain. {ECO:0000269|PubMed:12219086}.

Miscellaneous: The reaction proceeds by a bi uni uni bi ping pong mechanism.

Miscellaneous: Was identified as a high-confidence drug target.

Similarity: Belongs to the pantothenate synthetase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
Taxonomy:		Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae; Mycobacterium; Mycobacterium tuberculosis complex.



Function:		Catalyzes the condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate. {ECO:0000269\|PubMed:11669627}.


Catalytic activity:		Reaction=(R)-pantoate + ATP + beta-alanine = (R)-pantothenate + AMP + diphosphate + H(+); Xref=Rhea:RHEA:10912, ChEBI:CHEBI:15378, ChEBI:CHEBI:15980, ChEBI:CHEBI:29032, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57966, ChEBI:CHEBI:456215; EC=6.3.2.1; Evidence={ECO:0000269\|PubMed:12717031};
Activity regulation:		Pantothenate exhibits uncompetitive inhibition toward both D-pantoate and ATP, and non-competitive inhibition toward beta-alanine. AMPCPP exhibits competitive inhibition toward ATP, uncompetitive inhibition toward beta-alanine, and non-competitive inhibition toward D-pantoate. The enzyme is most active in the presence of magnesium or manganese. Other divalent cations (cobalt, nickel, zinc) are less effective. {ECO:0000269\|PubMed:11669627}.
Biophysicochemical properties:		Kinetic parameters: KM=130 uM for D-pantoate {ECO:0000269\|PubMed:11669627, ECO:0000269\|PubMed:15170354}; KM=800 uM for beta-alanine {ECO:0000269\|PubMed:11669627, ECO:0000269\|PubMed:15170354}; KM=2600 uM for ATP {ECO:0000269\|PubMed:11669627, ECO:0000269\|PubMed:15170354}; KM=25.4 mM for 2-mercaptoethylamine {ECO:0000269\|PubMed:11669627, ECO:0000269\|PubMed:15170354}; KM=36 mM for carbamate {ECO:0000269\|PubMed:11669627, ECO:0000269\|PubMed:15170354}; KM=72 mM for 5-aminovalerate {ECO:0000269\|PubMed:11669627, ECO:0000269\|PubMed:15170354}; KM=79 mM for methylamine {ECO:0000269\|PubMed:11669627, ECO:0000269\|PubMed:15170354}; KM=84 mM for glycine {ECO:0000269\|PubMed:11669627, ECO:0000269\|PubMed:15170354}; KM=93 mM for ethylamine {ECO:0000269\|PubMed:11669627, ECO:0000269\|PubMed:15170354}; KM=103 mM for taurine {ECO:0000269\|PubMed:11669627, ECO:0000269\|PubMed:15170354}; KM=108 mM for glycolate {ECO:0000269\|PubMed:11669627, ECO:0000269\|PubMed:15170354}; KM=335 mM for gamma-aminobutyrate {ECO:0000269\|PubMed:11669627, ECO:0000269\|PubMed:15170354}; KM=580 mM for gamma-amino-beta-hydroxybutyrate {ECO:0000269\|PubMed:11669627, ECO:0000269\|PubMed:15170354};
Pathway:		Cofactor biosynthesis; (R)-pantothenate biosynthesis; (R)- pantothenate from (R)-pantoate and beta-alanine: step 1/1.
Subcellular location:		Cytoplasm {ECO:0000305}.
Mass spectrometry:		Mass=32545; Method=Electrospray; Evidence={ECO:0000269\|PubMed:11669627};
Disruption phenotype:		Simultaneous disruption of panD and panC gives a mutant unable to grow in the absence of panothenate. The double mutant has a highly attenuated disease response in BALB/c and SCID mice; immunocompromised BALB/c SCID mice survive on average 36 weeks as opposed to 5 weeks for mice infected with wild-type bacteria, while immunocompetent BALB/c mice survive indefinitely. In wild-type mice bacteria grow for 3 weeks then undergo a steady decline, bacteria persist over 8 months in SCID mice (PubMed:12219086). The double mutant is sensitive to PZA but not POA in liquid culture, beta-alanine but not pantothenate antagonize the effect of PZA at pH 5.8 (PubMed:25246400). {ECO:0000269\|PubMed:12219086, ECO:0000269\|PubMed:25246400}.
Biotechnology:		Subcutaneous immunization with the double panD and panC bacterial disruption mutant protects mice for over a year against subsequent virulent M.tuberculosis (strain Erdman) infections; mice show mild lung inflammation and fibrosis despite a chronic bacterila infection. This is a promising attenuated vaccine strain. {ECO:0000269\|PubMed:12219086}.
Miscellaneous:		The reaction proceeds by a bi uni uni bi ping pong mechanism.
Miscellaneous:		Was identified as a high-confidence drug target.
Similarity:		Belongs to the pantothenate synthetase family. {ECO:0000305}.