Information on EC 4.2.1.109 - methylthioribulose 1-phosphate dehydratase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY
4.2.1.109
-
RECOMMENDED NAME
GeneOntology No.
methylthioribulose 1-phosphate dehydratase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-methyl-5-thio-D-ribulose 1-phosphate = 5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
-
-
-
-
S-methyl-5-thio-D-ribulose 1-phosphate = 5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
active site architecture and catalytic mechanism, overview
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dehydration
O31668
-
dehydration
Bacillus subtilis 168 (trp C2)
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Cysteine and methionine metabolism
-
-
Metabolic pathways
-
-
methionine metabolism
-
-
S-methyl-5-thio-alpha-D-ribose 1-phosphate degradation
-
-
SYSTEMATIC NAME
IUBMB Comments
S-methyl-5-thio-D-ribulose-1-phosphate 4-hydro-lyase [5-(methylthio)-2,3-dioxopentyl-phosphate-forming]
This enzyme forms part of the methionine-salvage pathway.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
1-PMT-ribulose dehydratase
-
-
5'-methylthioribulose-1-phosphate dehydratase
Q96GX9
-
5-Methylthioribulose-1-phosphate
O31668
-
5-Methylthioribulose-1-phosphate
Bacillus subtilis 168 (trp C2)
O31668
-
-
5-methylthioribulose-1-phosphate dehydratase
Q96GX9
-
5-methylthioribulose-1-phosphate dehydratase
P47095
-
Apaf-1 interacting protein
Q96GX9
-
Apaf-1-interacting protein
Q96GX9
-
MtnB
O31668
-
MtnB
Bacillus subtilis 168 (trp C2)
O31668
-
-
MtnB
Q96GX9
-
MtnBD
I7MAL0
gene name
MTRu-1-P dehydratase
O31668
-
MTRu-1-P dehydratase
Bacillus subtilis 168 (trp C2)
O31668
-
-
MTRu-1-P dehydratase/enolase
I7MAL0
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain 168 (trp C2)
TrEMBL
Manually annotated by BRENDA team
Bacillus subtilis 168 (trp C2)
strain 168 (trp C2)
TrEMBL
Manually annotated by BRENDA team
gene mtnB
UniProt
Manually annotated by BRENDA team
gene Yjr024cp by homology comparison
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
I7MAL0
the MtnB domain of Tetrahymena thermophila MtnBD acquired the new function to catalyze both the dehydratase and enolase reactions through evolutionary gene mutations, rather than fusion of MSP genes
malfunction
Q96GX9
the enzyme depletion specifically impairs the capacity of cells to grow in media where methionine is replaced by 5-methylthioadenosine. Knockdown of the enzyme specifically affects the recycling of methionine, and mutation of three potential phosphorylation sites does not affect the enzyme activity whereas mutation of the potential zinc binding site completely abrogates it
metabolism
Q96GX9
the enzyme catalyzes the dehydratase step in the methionine salvage pathway
metabolism
-
the enzyme is involved in the methionine salvage pathway
physiological function
-
Apaf-1-interacting protein (APIP) is known to inhibit two different types of cell death: caspase-1-dependent pyroptosis and caspase-9-dependent apoptosis. The enzyme is also involved in the methionine-salvage pathway, where it is called 5-methylthioribulose-1-phosphate dehydratase (MtnB). The enzyme activity seems to be essential for inhibition of pyroptosis by the enzyme, but not for inhibition of apoptosis, overview
physiological function
-
the enzyme Apaf-1 interacting protein/5-methylthioribulose-1-phosphate dehydratase has two distinct functions, cell death inhibition and methionine salvage. It functions as a cell death inhibitor independently of its MtnB enzyme activity for apoptosis, but dependently for caspase-1-induced pyroptosis. Pyroptosis inhibition by the Apaf-1 interacting protein is dependent upon its MtnB enzyme activity. Role of Apaf-1 interacting protein/5-methylthioribulose-1-phosphate dehydratase in development of cancers and inflammatory diseases. The enzyme acts as an inhibitor of caspase-9-dependent apoptosis induced by ischemic/hypoxic injury or by cytotoxic agents such as etoposide and cisplatin
physiological function
Q96GX9
the enzyme is involved in the methionine salvage pathway that recycles the sulfur-containing metabolite 5-methylthioadenosine to methionine
metabolism
I7MAL0
the MtnBD fusion enzyme in Tetrahymena thermophila catalyzes two of the sequential reactions from the dehydratase to dioxygenase steps in the methionine salvage pathway: 5-methylthioribulose-1-phosphate is converted to 2-oxo-4-methylthiobutyrate, the methionine precursor, by four steps, namely dehydratase, enolase, phosphatase, and dioxygenase reactions. The MtnB domain catalyzes dehydration and enolization and the MtnD domain catalyzes dioxygenation, the phosphatase is distinct from the enzyme. Methionine salvage pathway, overview
additional information
-
active site architecture and catalytic mechanism, overview
additional information
I7MAL0
identification of the domains responsible for catalyzing the four reactions from the enzyme, overview
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
-
-
-
-
?
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
-
-
-
-
?
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
O31668
-
-
-
?
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
O31668
-
the reaction product 5-(methylthio)-2,3-dioxopentyl phosphate is so labile that its chemical structure could not be isolated and analyzed
-
?
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
P47095
enzyme of the methionine salvage pathway
-
-
?
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
-
the enzyme forms part of the methionine-salvage pathway
-
-
?
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
I7MAL0
activity of the MtnB domain
-
-
?
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
-
substrate-binding mode, overview
-
-
?
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
Bacillus subtilis 168 (trp C2)
O31668
-
the reaction product 5-(methylthio)-2,3-dioxopentyl phosphate is so labile that its chemical structure could not be isolated and analyzed
-
?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
O31668
-
-
-
?
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
P47095
enzyme of the methionine salvage pathway
-
-
?
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
-
the enzyme forms part of the methionine-salvage pathway
-
-
?
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
I7MAL0
activity of the MtnB domain
-
-
?
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
-
substrate-binding mode, overview
-
-
?
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
show the reaction diagram
Bacillus subtilis 168 (trp C2)
O31668
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
Q96GX9
required by the enzyme protein
Zn2+
-
near the zinc ion, the surface of the active site pocket is formed by several residues, including Cys97, Tyr198, Glu139, Lys142, and Asn166. Residues Cys97, Glu139, and Tyr198 form hydrogen bonds with the three water molecules that coordinate the zinc ion
additional information
O31668
MtnB requires metal ions for catalysis, but it is unclear what kind of metal ions are bound to the MtnB purified from Escherichia coli cells. Considering that FucA/RibE/RhuA-related enzymes require the zinc ion for optimal catalysis under physiological conditions and that recombinant class II aldolase enzymes expressed in Escherichia coli cells are almost all of the Zn2+ form, purified MtnB might also be of the Zn2+ form
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0089
S-methyl-5-thio-D-ribulose 1-phosphate
O31668
25C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
16.5
S-methyl-5-thio-D-ribulose 1-phosphate
O31668
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5 - 8
O31668
-
7.5
-
assay at
8
I7MAL0
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5 - 10.5
O31668
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
35
I7MAL0
assay at
40
O31668
at 55C the enzyme loses most of its activity
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
15 - 55
O31668
at 55C the enzyme loses most of its activity
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
90000
O31668
without His-tag, 4 * 23800, SDS-PAGE
691391
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homotetramer
O31668
4 * 23800
homotetramer
Bacillus subtilis 168 (trp C2)
-
4 * 23800
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified recombinant His-tagged enzyme fragment of residues 20-242, hanging drop vapour diffusion method, 0.001 ml of protein solution, containing 20 mM Tris-HCl, 5% v/v glycerol, 0.1 mM TCEP, 100 mM sodium chloride, pH 8.0, is mixed with 0.001 ml of reservoir solution, containing 0.04 M citric acid, 0.06 M Bis-Tris propane, 5% v/v glycerol, 18-21% w/v PEG 3350, and equilibrated against 0.2 ml of reservoir solution, 22C, 5 days to 2 weeks, X-ray diffraction structure determination and analysis at 2.40 A resolution
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
homogeneity, using the His-tag, the His-tag is cleaved with thrombin
O31668
recombinant His-tagged enzyme residues 20-242 from Escherichia coli strain Rosetta 2(DE3) by metal affinity chhromatography, anion exchange chromatography, gel filtration, and ultrafiltration
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed as (His)6-tagged soluble protein in Escherichia BL21 (DE3), vector pET15b
O31668
recombinant overexpression of an His-tagged enzyme fragment comprising the residues 20-242 in Escherichia coli strain Rosetta 2(DE3)
-
gene mtnBD, identification of the domains responsible for catalyzing the four reactions from the enzyme, overview. Recombinant expression of His-tagged proteins of full-length enzyme and the MtnB domain in Escherichia coli BL21(DE3)
I7MAL0
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D72A
-
site-directed mutagenesis, the mutant shows similar levels of pyroptosis inhibition and apoptosis inhibition as the wild-type enzyme
D72A/K90A
-
site-directed mutagenesis, the mutant shows a similar level of pyroptosis inhibition as the wild-type enzyme, but a significant loss of apoptosis inhibition activity
P185A
-
site-directed mutagenesis, the mutant shows similar levels of pyroptosis inhibition and apoptosis inhibition as the wild-type enzyme
Y184A
-
site-directed mutagenesis, the mutant shows similar levels of pyroptosis inhibition and apoptosis inhibition as the wild-type enzyme
Y184A/P185A
-
site-directed mutagenesis, the mutant shows similar levels of pyroptosis inhibition and apoptosis inhibition as the wild-type enzyme
K90A
-
site-directed mutagenesis, the mutant shows a similar level of pyroptosis inhibition as the wild-type enzyme, but a significant loss of apoptosis inhibition activity
additional information
Q96GX9
transient silencing of the enzyme in HeLa cells. Stable knockdown of the enzyme specifically affects growth in 5-methylthioadenosine and depletes intracellular levels of methionine