UniProt functional annotation for P9WFX1



	UniProt functional annotation for P9WFX1

UniProt code: P9WFX1.

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

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

Function: Involved in the incorporation of salicylate into the virulence-conferring salicylate-based siderophore mycobactin. Catalyzes the initial conversion of chorismate to yield the intermediate isochorismate (isochorismate synthase activity), and the subsequent elimination of the enolpyruvyl side chain to give salicylate (isochorismate pyruvate-lyase activity). In the absence of magnesium, MbtI displays a chorismate mutase activity and converts chorismate to prephenate. {ECO:0000269|PubMed:16923875, ECO:0000269|PubMed:17240979, ECO:0000269|PubMed:20487026, ECO:0000269|PubMed:20512795, ECO:0000269|PubMed:9831524}.

Catalytic activity: Reaction=chorismate = isochorismate; Xref=Rhea:RHEA:18985, ChEBI:CHEBI:29748, ChEBI:CHEBI:29780; EC=5.4.4.2; Evidence={ECO:0000269|PubMed:16923875, ECO:0000269|PubMed:17240979, ECO:0000269|PubMed:20512795};

Catalytic activity: Reaction=isochorismate = pyruvate + salicylate; Xref=Rhea:RHEA:27874, ChEBI:CHEBI:15361, ChEBI:CHEBI:29780, ChEBI:CHEBI:30762; EC=4.2.99.21; Evidence={ECO:0000269|PubMed:16923875, ECO:0000269|PubMed:17240979, ECO:0000269|PubMed:20512795};

Catalytic activity: Reaction=chorismate = prephenate; Xref=Rhea:RHEA:13897, ChEBI:CHEBI:29748, ChEBI:CHEBI:29934; EC=5.4.99.5; Evidence={ECO:0000269|PubMed:17240979};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:16923875, ECO:0000269|PubMed:17240979, ECO:0000269|PubMed:20512795};

Activity regulation: Inhibited by (E)-3-(1-carboxyprop-1-enyloxy)-2- hydroxybenzoic acid (AMT), 3-(1-carboxy-2-phenylvinyloxy)-2- hydroxybenzoic acid (phenyl-AMT), 3-(1-carboxy-3-methylbut-1-enyloxy)- 2-hydroxybenzoic acid, 3-(1-carboxybut-1-enyloxy)-2-hydroxybenzoic acid (ethyl-AMT), 3-(1-carboxyprop-1-enyloxy)-2-hydroxybenzoic acid (methyl- AMT), 3-(1-carboxy-2-cyclopropylethenyloxy)-2-hydroxybenzoic acid (cyclopropyl-AMT) and 3-(1-carboxy-3-methylbut-1-enyloxy)-2- hydroxybenzoic acid (isopropyl-AMT). {ECO:0000269|PubMed:20512795, ECO:0000269|PubMed:22607697}.

Biophysicochemical properties: Kinetic parameters: KM=2.6 uM for isochorismate (for isochorismate pyruvate lyase activity at pH 8 and 37 degrees Celsius) {ECO:0000269|PubMed:17240979}; KM=6 uM for isochorismate (for salicylate synthase activity at pH 8 and 37 degrees Celsius) {ECO:0000269|PubMed:17240979}; KM=21 uM for isochorismate (for salicylate synthase activity at pH 8 and 25 degrees Celsius) {ECO:0000269|PubMed:20512795}; KM=26 uM for chorismate (for chorismate mutase activity without magnesium at pH 7.5 and 37 degrees Celsius) {ECO:0000269|PubMed:17240979}; KM=34 uM for chorismate (for isochorismate synthase activity at pH 7 and 37 degrees Celsius) {ECO:0000269|PubMed:17240979}; Note=Kcat is 2.6 min(-1) for isochorismate pyruvate lyase activity (at pH 8 and 37 degrees Celsius). Kcat is 2.8 min(-1) for salicylate synthase activity (at pH 8 and 37 degrees Celsius). Kcat is 3.1 min(- 1) for isochorismate synthase activity (at pH 7 and 37 degrees Celsius). Kcat is 4.5 min(-1) for chorismate mutase activity (without magnesium at pH 7.5 and 37 degrees Celsius). {ECO:0000269|PubMed:17240979}; pH dependence: At pH below 7.5, MtbI produces isochorismate and at pH 8 it produces salicylate. {ECO:0000269|PubMed:17240979};

Pathway: Siderophore biosynthesis; mycobactin biosynthesis. {ECO:0000305|PubMed:9831524}.

Subunit: Monomer. {ECO:0000269|PubMed:16508110, ECO:0000269|PubMed:16923875, ECO:0000269|PubMed:17240979, ECO:0000269|PubMed:20512795, ECO:0000269|PubMed:22607697}.

Induction: Induced by iron starvation conditions and during infection of human THP-1 macrophages. Transcriptionally repressed by IdeR and iron. {ECO:0000269|PubMed:11722747}.

Disruption phenotype: Cells lacking this gene display a reduction in salicylic acid biosynthesis and a drastic decrease in production of mycobactin compared with the wild-type strain. {ECO:0000269|PubMed:20487026}.

Similarity: Belongs to the anthranilate synthase component I family. Salicylate synthase subfamily. {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:		Involved in the incorporation of salicylate into the virulence-conferring salicylate-based siderophore mycobactin. Catalyzes the initial conversion of chorismate to yield the intermediate isochorismate (isochorismate synthase activity), and the subsequent elimination of the enolpyruvyl side chain to give salicylate (isochorismate pyruvate-lyase activity). In the absence of magnesium, MbtI displays a chorismate mutase activity and converts chorismate to prephenate. {ECO:0000269\|PubMed:16923875, ECO:0000269\|PubMed:17240979, ECO:0000269\|PubMed:20487026, ECO:0000269\|PubMed:20512795, ECO:0000269\|PubMed:9831524}.


Catalytic activity:		Reaction=chorismate = isochorismate; Xref=Rhea:RHEA:18985, ChEBI:CHEBI:29748, ChEBI:CHEBI:29780; EC=5.4.4.2; Evidence={ECO:0000269\|PubMed:16923875, ECO:0000269\|PubMed:17240979, ECO:0000269\|PubMed:20512795};
Catalytic activity:		Reaction=isochorismate = pyruvate + salicylate; Xref=Rhea:RHEA:27874, ChEBI:CHEBI:15361, ChEBI:CHEBI:29780, ChEBI:CHEBI:30762; EC=4.2.99.21; Evidence={ECO:0000269\|PubMed:16923875, ECO:0000269\|PubMed:17240979, ECO:0000269\|PubMed:20512795};
Catalytic activity:		Reaction=chorismate = prephenate; Xref=Rhea:RHEA:13897, ChEBI:CHEBI:29748, ChEBI:CHEBI:29934; EC=5.4.99.5; Evidence={ECO:0000269\|PubMed:17240979};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:16923875, ECO:0000269\|PubMed:17240979, ECO:0000269\|PubMed:20512795};
Activity regulation:		Inhibited by (E)-3-(1-carboxyprop-1-enyloxy)-2- hydroxybenzoic acid (AMT), 3-(1-carboxy-2-phenylvinyloxy)-2- hydroxybenzoic acid (phenyl-AMT), 3-(1-carboxy-3-methylbut-1-enyloxy)- 2-hydroxybenzoic acid, 3-(1-carboxybut-1-enyloxy)-2-hydroxybenzoic acid (ethyl-AMT), 3-(1-carboxyprop-1-enyloxy)-2-hydroxybenzoic acid (methyl- AMT), 3-(1-carboxy-2-cyclopropylethenyloxy)-2-hydroxybenzoic acid (cyclopropyl-AMT) and 3-(1-carboxy-3-methylbut-1-enyloxy)-2- hydroxybenzoic acid (isopropyl-AMT). {ECO:0000269\|PubMed:20512795, ECO:0000269\|PubMed:22607697}.
Biophysicochemical properties:		Kinetic parameters: KM=2.6 uM for isochorismate (for isochorismate pyruvate lyase activity at pH 8 and 37 degrees Celsius) {ECO:0000269\|PubMed:17240979}; KM=6 uM for isochorismate (for salicylate synthase activity at pH 8 and 37 degrees Celsius) {ECO:0000269\|PubMed:17240979}; KM=21 uM for isochorismate (for salicylate synthase activity at pH 8 and 25 degrees Celsius) {ECO:0000269\|PubMed:20512795}; KM=26 uM for chorismate (for chorismate mutase activity without magnesium at pH 7.5 and 37 degrees Celsius) {ECO:0000269\|PubMed:17240979}; KM=34 uM for chorismate (for isochorismate synthase activity at pH 7 and 37 degrees Celsius) {ECO:0000269\|PubMed:17240979}; Note=Kcat is 2.6 min(-1) for isochorismate pyruvate lyase activity (at pH 8 and 37 degrees Celsius). Kcat is 2.8 min(-1) for salicylate synthase activity (at pH 8 and 37 degrees Celsius). Kcat is 3.1 min(- 1) for isochorismate synthase activity (at pH 7 and 37 degrees Celsius). Kcat is 4.5 min(-1) for chorismate mutase activity (without magnesium at pH 7.5 and 37 degrees Celsius). {ECO:0000269\|PubMed:17240979}; pH dependence: At pH below 7.5, MtbI produces isochorismate and at pH 8 it produces salicylate. {ECO:0000269\|PubMed:17240979};
Pathway:		Siderophore biosynthesis; mycobactin biosynthesis. {ECO:0000305\|PubMed:9831524}.
Subunit:		Monomer. {ECO:0000269\|PubMed:16508110, ECO:0000269\|PubMed:16923875, ECO:0000269\|PubMed:17240979, ECO:0000269\|PubMed:20512795, ECO:0000269\|PubMed:22607697}.
Induction:		Induced by iron starvation conditions and during infection of human THP-1 macrophages. Transcriptionally repressed by IdeR and iron. {ECO:0000269\|PubMed:11722747}.
Disruption phenotype:		Cells lacking this gene display a reduction in salicylic acid biosynthesis and a drastic decrease in production of mycobactin compared with the wild-type strain. {ECO:0000269\|PubMed:20487026}.
Similarity:		Belongs to the anthranilate synthase component I family. Salicylate synthase subfamily. {ECO:0000305}.