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Information on EC 4.2.99.21 - isochorismate lyase and Organism(s) Mycobacterium tuberculosis and UniProt Accession P9WFX1

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EC Tree
     4 Lyases
         4.2 Carbon-oxygen lyases
             4.2.99 Other carbon-oxygen lyases
                4.2.99.21 isochorismate lyase
IUBMB Comments
This enzyme is part of the pathway of salicylate formation from chorismate, and forms an integral part of pathways that produce salicylate-derived siderophores, such as pyochelin and yersiniabactin.
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This record set is specific for:
Mycobacterium tuberculosis
UNIPROT: P9WFX1
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Word Map
The taxonomic range for the selected organisms is: Mycobacterium tuberculosis
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
isochorismate pyruvate lyase, isochorismate-pyruvate lyase, isochorismate lyase, prxr1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
salicylate synthase
EC 5.4.4.2 and 4.2.99.21
pyochelin biosynthetic protein PchB
-
-
-
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isochorismate pyruvate lyase
-
-
-
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salicylate biosynthesis protein pchB
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-
-
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salicylate synthase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
isochorismate = salicylate + pyruvate
show the reaction diagram
SYSTEMATIC NAME
IUBMB Comments
isochorismate pyruvate-lyase (salicylate-forming)
This enzyme is part of the pathway of salicylate formation from chorismate, and forms an integral part of pathways that produce salicylate-derived siderophores, such as pyochelin and yersiniabactin.
CAS REGISTRY NUMBER
COMMENTARY hide
383896-77-3
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
isochorismate
salicylate + pyruvate
show the reaction diagram
-
-
-
?
isochorismate
salicylate + pyruvate
show the reaction diagram
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-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
isochorismate
salicylate + pyruvate
show the reaction diagram
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
-
the salicylate and isochorismate synthase activities of MbtI are Mg2+-dependent, and in the absence of Mg2+, MbtI has a promiscuous chorismate mutase activity similar to that of the isochorismate pyruvate lyase, PchB, from Pseudomonas aeruginosa
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(4R,5R)-5-[(1-carboxyethenyl)oxy]-4-hydroxycyclohex-1-ene-1-carboxylic acid
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1-(2-sulfanylidene-2,3-dihydro-1H-benzimidazol-1-yl)ethan-1-one
-
3-(1-carboxyethoxy)-4,5-dihydroxybenzoic acid
-
3-(3,4-dichlorobenzene-1-sulfonyl)benzene-1-sulfonamide
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3-([(E)-1-carboxy-2-[2-(trifluoromethyl)phenyl]ethenyl]oxy)-2-hydroxybenzoic acid
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3-([(E)-1-carboxy-2-[3-(trifluoromethyl)phenyl]ethenyl]oxy)-2-hydroxybenzoic acid
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3-([(E)-1-carboxy-2-[4-(trifluoromethyl)phenyl]ethenyl]oxy)-2-hydroxybenzoic acid
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3-([(E)-2-[2-(acetyloxy)phenyl]-1-carboxyethenyl]oxy)-2-hydroxybenzoic acid
-
3-([(E)-2-[3-(acetyloxy)phenyl]-1-carboxyethenyl]oxy)-2-hydroxybenzoic acid
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3-([(E)-2-[4-(acetyloxy)phenyl]-1-carboxyethenyl]oxy)-2-hydroxybenzoic acid
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3-[(1-carboxyethenyl)oxy]-4,5-dihydroxybenzoic acid
-
3-[(1-carboxyethenyl)oxy]-4-hydroxybenzoic acid
-
3-[(1-carboxyethenyl)oxy]benzoic acid
-
3-[(2-carboxyprop-2-en-1-yl)oxy]-4,5-dihydroxybenzoic acid
-
3-[[(1E)-1-carboxy-3-methylbut-1-en-1-yl]oxy]-4-hydroxybenzoic acid
-
3-[[(1E)-1-carboxy-3-methylbut-1-en-1-yl]oxy]benzoic acid
-
3-[[(1E)-1-carboxybut-1-en-1-yl]oxy]benzoic acid
-
3-[[(1E)-1-carboxyprop-1-en-1-yl]oxy]-2-hydroxybenzoic acid
-
3-[[(1E)-1-carboxyprop-1-en-1-yl]oxy]-4-hydroxybenzoic acid
-
3-[[(1E)-1-carboxyprop-1-en-1-yl]oxy]benzoic acid
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3-[[(E)-1-carboxy-2-(2-chlorophenyl)ethenyl]oxy]-2-hydroxybenzoic acid
-
3-[[(E)-1-carboxy-2-(2-methylphenyl)ethenyl]oxy]-2-hydroxybenzoic acid
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3-[[(E)-1-carboxy-2-(3-chlorophenyl)ethenyl]oxy]-2-hydroxybenzoic acid
-
3-[[(E)-1-carboxy-2-(3-methylphenyl)ethenyl]oxy]-2-hydroxybenzoic acid
-
3-[[(E)-1-carboxy-2-(4-chlorophenyl)ethenyl]oxy]-2-hydroxybenzoic acid
-
3-[[(E)-1-carboxy-2-(4-methylphenyl)ethenyl]oxy]-2-hydroxybenzoic acid
-
3-[[(E)-1-carboxy-2-phenylethenyl]oxy]-2-hydroxybenzoic acid
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3-[[(E)-1-carboxy-2-phenylethenyl]oxy]-4-hydroxybenzoic acid
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3-[[(E)-1-carboxy-2-phenylethenyl]oxy]benzoic acid
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3-[[(E)-2-(2-bromophenyl)-1-carboxyethenyl]oxy]-2-hydroxybenzoic acid
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3-[[(E)-2-(3-bromophenyl)-1-carboxyethenyl]oxy]-2-hydroxybenzoic acid
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3-[[(E)-2-(4-bromophenyl)-1-carboxyethenyl]oxy]-2-hydroxybenzoic acid
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methyl 2-hydroxy-3-([(1E)-3-methoxy-3-oxo-1-[2-(trifluoromethyl)phenyl]prop-1-en-2-yl]oxy)benzoate
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methyl 2-hydroxy-3-([(1E)-3-methoxy-3-oxo-1-[3-(trifluoromethyl)phenyl]prop-1-en-2-yl]oxy)benzoate
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methyl 2-hydroxy-3-([(1E)-3-methoxy-3-oxo-1-[4-(trifluoromethyl)phenyl]prop-1-en-2-yl]oxy)benzoate
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methyl 2-hydroxy-3-[[(1E)-3-methoxy-1-(2-methylphenyl)-3-oxoprop-1-en-2-yl]oxy]benzoate
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methyl 2-hydroxy-3-[[(1E)-3-methoxy-1-(3-methylphenyl)-3-oxoprop-1-en-2-yl]oxy]benzoate
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methyl 2-hydroxy-3-[[(1E)-3-methoxy-1-(4-methylphenyl)-3-oxoprop-1-en-2-yl]oxy]benzoate
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methyl 3-([(1E)-1-[2-(acetyloxy)phenyl]-3-methoxy-3-oxoprop-1-en-2-yl]oxy)-2-hydroxybenzoate
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methyl 3-([(1E)-1-[3-(acetyloxy)phenyl]-3-methoxy-3-oxoprop-1-en-2-yl]oxy)-2-hydroxybenzoate
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methyl 3-([(1E)-1-[4-(acetyloxy)phenyl]-3-methoxy-3-oxoprop-1-en-2-yl]oxy)-2-hydroxybenzoate
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methyl 3-[[(1E)-1-(2-bromophenyl)-3-methoxy-3-oxoprop-1-en-2-yl]oxy]-2-hydroxybenzoate
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methyl 3-[[(1E)-1-(2-chlorophenyl)-3-methoxy-3-oxoprop-1-en-2-yl]oxy]-2-hydroxybenzoate
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methyl 3-[[(1E)-1-(3-bromophenyl)-3-methoxy-3-oxoprop-1-en-2-yl]oxy]-2-hydroxybenzoate
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methyl 3-[[(1E)-1-(3-chlorophenyl)-3-methoxy-3-oxoprop-1-en-2-yl]oxy]-2-hydroxybenzoate
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methyl 3-[[(1E)-1-(4-bromophenyl)-3-methoxy-3-oxoprop-1-en-2-yl]oxy]-2-hydroxybenzoate
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methyl 3-[[(1E)-1-(4-chlorophenyl)-3-methoxy-3-oxoprop-1-en-2-yl]oxy]-2-hydroxybenzoate
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N-ethyl-3-(3-oxo-1,2-benzothiazol-2(3H)-yl)benzene-1-sulfonamide
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(E)-3-(1-carboxyprop-1-enyloxy)-2-hydroxybenzoic acid
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low micromolar inhibition of both isochorismate lyase and anthranilate synthase
3-(1-carboxy-2-phenylvinyloxy)-2-hydroxybenzoic acid
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low micromolar inhibition of both isochorismate lyase and anthranilate synthase
3-(1-carboxy-3-methylbut-1-enyloxy)-2-hydroxybenzoic acid
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low micromolar inhibition of both isochorismate lyase and anthranilate synthase
3-(1-carboxybut-1-enyloxy)-2-hydroxybenzoic acid
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low micromolar inhibition of both isochorismate lyase and anthranilate synthase
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0021 - 0.0026
isochorismate
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.035 - 0.8
isochorismate
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
13.5
isochorismate
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pH 7.0, 37°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.4
3-(1-carboxyethoxy)-4,5-dihydroxybenzoic acid
pH and temperature not specified in the publication
1.7
3-[(1-carboxyethenyl)oxy]-4,5-dihydroxybenzoic acid
pH and temperature not specified in the publication
3
3-[(2-carboxyprop-2-en-1-yl)oxy]-4,5-dihydroxybenzoic acid
pH and temperature not specified in the publication
0.013
(E)-3-(1-carboxyprop-1-enyloxy)-2-hydroxybenzoic acid
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pH 8.0, 25°C
0.021
3-(1-carboxy-2-phenylvinyloxy)-2-hydroxybenzoic acid
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pH 8.0, 25°C
0.014
3-(1-carboxy-3-methylbut-1-enyloxy)-2-hydroxybenzoic acid
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pH 8.0, 25°C
0.012
3-(1-carboxybut-1-enyloxy)-2-hydroxybenzoic acid
-
pH 8.0, 25°C
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
at pH values below 7.5 isochorismate is the dominant product while above this pH value the enzyme converts chorismate to salicylate without the accumulation of isochorismate in solution
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
physiological function
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
docking studies of inhibitors (E)-3-(1-carboxyprop-1-enyloxy)-2-hydroxybenzoic acid, 3-(1-carboxy-3-methylbut-1-enyloxy)-2-hydroxybenzoic acid, 3-(1-carboxybut-1-enyloxy)-2-hydroxybenzoic acid, and 3-(1-carboxy-2-phenylvinyloxy)-2-hydroxybenzoic acid
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native protein and selenomethionine-derivative, to 2.5-3.2 A resolution
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
enzyme MbtI represents an appealing target for development of inhibitors of mycobactin biosynthesis since it is structurally and biochemically characterized, has no human orthologues, and is conditionally essential under iron-deficient conditions. Inhibitors are designed against the isochorismatase activity of the enzyme (EC 5.4.4.2)
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Zwahlen, J.; Kolappan, S.; Zhou, R.; Kisker, C.; Tonge, P.J.
Structure and mechanism of MbtI, the salicylate synthase from Mycobacterium tuberculosis
Biochemistry
46
954-964
2007
Mycobacterium tuberculosis
Manually annotated by BRENDA team
Manos-Turvey, A.; Bulloch, E.M.M.; Rutledge, P.J.; Baker, E.N.; Lott, J.S.; Payne, R.J.
Inhibition studies of Mycobacterium tuberculosis salicylate synthase (MbtI)
ChemMedChem
5
1067-1079
2010
Mycobacterium tuberculosis
Manually annotated by BRENDA team
Svarcova, M.; Kratky, M.; Vinsova, J.
Investigation of potential inhibitors of chorismate-utilizing enzymes
Curr. Med. Chem.
22
1383-1399
2015
Mycobacterium tuberculosis (P9WFX1), Mycobacterium tuberculosis ATCC 25618 (P9WFX1), no activity in Homo sapiens, Pseudomonas aeruginosa (Q51507), Pseudomonas aeruginosa ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1 (Q51507), Yersinia enterocolitica, Yersinia pestis
Manually annotated by BRENDA team
Liu, Z.; Liu, F.; Aldrich, C.C.
Stereocontrolled synthesis of a potential transition-state inhibitor of the salicylate synthase MbtI from Mycobacterium tuberculosis
J. Org. Chem.
80
6545-6552
2015
Mycobacterium tuberculosis (P9WFX1), Mycobacterium tuberculosis ATCC 25618 (P9WFX1)
Manually annotated by BRENDA team