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Information on EC 4.2.1.109 - methylthioribulose 1-phosphate dehydratase and Organism(s) Homo sapiens and UniProt Accession Q96GX9
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4.2.1.109 methylthioribulose 1-phosphate dehydrataseIUBMB Comments
This enzyme forms part of the methionine-salvage pathway.
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Word Map
- 4.2.1.109
-
salvage
- caspase-9
- dioxygenase
- 5-methylthioadenosine
-
aci-reductone
-
enolization
- tetrahymena
- etoposide
-
pyroptosis
- apoptosome
- thermophila
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
mtnbd, apaf-1-interacting protein, 5-methylthioribulose-1-phosphate, apaf-1 interacting protein, 5'-methylthioribulose-1-phosphate dehydratase, 5-methylthioribulose-1-phosphate dehydratase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
5-(methylsulfanyl)-D-ribulose 1-phosphate = 5-(methylsulfanyl)-2,3-dioxopentyl phosphate + H2O
active site architecture and catalytic mechanism, overview
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.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
substrate-binding mode, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-methyl-5-thio-D-ribulose 1-phosphate
5-(methylthio)-2,3-dioxopentyl phosphate + H2O
substrate-binding mode, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
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
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
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
physiological function
additional information
metabolism
the enzyme catalyzes the dehydratase step 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
the enzyme is involved in the methionine salvage pathway that recycles the sulfur-containing metabolite 5-methylthioadenosine to methionine
additional information
active site architecture and catalytic mechanism, overview
additional information
-
active site architecture and catalytic mechanism, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MTNB_HUMAN
242
0
27125
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
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, 22°C, 5 days to 2 weeks, X-ray diffraction structure determination and analysis at 2.40 A resolution
PROTEIN VARIANTS
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
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
additional information
additional information
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
additional information
-
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
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
recombinant overexpression of an His-tagged enzyme fragment comprising the residues 20-242 in Escherichia coli strain Rosetta 2(DE3)
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Mary, C.; Duek, P.; Salleron, L.; Tienz, P.; Bumann, D.; Bairoch, A.; Lane, L.
Functional identification of APIP as human mtnB, a key enzyme in the methionine salvage pathway
PLoS ONE
7
e52877
2012
Homo sapiens (Q96GX9), Homo sapiens
Kang, W.; Yang, J.K.
Crystallization and preliminary X-ray crystallographic analysis of human Apaf-1-interacting protein
Acta Crystallogr. Sect. F
68
1518-1520
2012
Homo sapiens (Q96GX9), Homo sapiens
Kang, W.; Hong, S.H.; Lee, H.M.; Kim, N.Y.; Lim, Y.C.; Le, L.T.M.; Lim, B.; Kim, H.C.; Kim, T.Y.; Ashida, H.; Yokota, A.; Hah, S.S.; Chun, K.H.; Jung, Y.K.; Yang, J.K.
Structural and biochemical basis for the inhibition of cell death by APIP, a methionine salvage enzyme
Proc. Natl. Acad. Sci. USA
111
E54-E61
2014
Homo sapiens (Q96GX9), Homo sapiens
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