Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 3.1.1.98 - [Wnt protein] O-palmitoleoyl-L-serine hydrolase and Organism(s) Homo sapiens

for references in articles please use BRENDA:EC3.1.1.98
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
IUBMB Comments
The enzyme removes the palmitoleate modification that is introduced to specific L-serine residues in Wnt proteins by EC 2.3.1.250, [Wnt protein]-O-palmitoleoyl transferase.
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
hide
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
hide
[Wnt]-O-(9Z)-hexadec-9-enoyl-L-serine
+
H2O
=
[Wnt]-L-serine
+
(9Z)-hexadec-9-enoate
[Wnt]-O-(9Z)-hexadec-9-enoyl-L-serine
+
=
[Wnt]-L-serine
+
Synonyms
notum, notum 1a, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Notum
SYSTEMATIC NAME
IUBMB Comments
[Wnt]-O-(9Z)-hexadec-9-enoyl-L-serine acylhydrolase
The enzyme removes the palmitoleate modification that is introduced to specific L-serine residues in Wnt proteins by EC 2.3.1.250, [Wnt protein]-O-palmitoleoyl transferase.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
4-nitrophenyl acetate + H2O
4-nitrophenol + acetate
show the reaction diagram
-
-
-
?
[Wnt]-O-(9Z)-hexadec-9-enoyl-L-serine + H2O
[Wnt]-L-serine + (9Z)-hexadec-9-enoate
show the reaction diagram
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
[Wnt]-O-(9Z)-hexadec-9-enoyl-L-serine + H2O
[Wnt]-L-serine + (9Z)-hexadec-9-enoate
show the reaction diagram
the enzyme removes the palmitoleate modification that is introduced to specific L-serine residues in Wnt proteins by [Wnt protein]-O-palmitoleoyl transferase
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-[(2,3-dihydro-4H-1,4-benzoxazine-4-carbonyl)oxy]-7-[(6-phenoxypyridin-3-yl)methyl]tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione
-
7-(4-chlorobenzoyl)-2-[(2,3-dihydro-4H-1,4-benzoxazine-4-carbonyl)oxy]tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione
-
7-(4-chlorobenzyl)-1,3-dioxohexahydroimidazo[1,5-a]pyrazin-2(3H)-yl 2,3-dihydro-4Hbenzo[b][1,4]oxazine-4-carboxylate
i.e. ABC99, selective irreversible inhibitor. The optimized -hydroxyhydantoin carbamate inhibitor preserves Wnt-mediated cell signaling in the presence of NOTUM and is also converted into an ABPP probe for visualizing NOTUM in native biological systems
7-[(2-chlorophenyl)methyl]-2-([4-(4-methoxyphenyl)piperazine-1-carbonyl]oxy)tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione
-
7-[(3-chlorophenyl)methyl]-2-([4-(4-methoxyphenyl)piperazine-1-carbonyl]oxy)tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione
-
7-[(4-bromophenyl)methyl]-2-[[4-(4-methoxyphenyl)piperazine-1-carbonyl]oxy]tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione
-
7-[(4-chlorophenyl)methyl]-2-([4-(4-methoxyphenyl)piperazine-1-carbonyl]oxy)tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione
-
7-[(4-chlorophenyl)methyl]-2-[(2,3-dihydro-4H-1,4-benzoxazine-4-carbonyl)oxy]tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione
the optimized N-hydroxyhydantoin carbamate inhibitor preserves Wnt-mediated cell signaling in the presence of NOTUM and is also converted into an activity-based protein profiling (ABPP) probe for visualizing NOTUM in native biological systems. NOTUM inhibitors have potential for treating degenerative diseases
Phenylmethanesulfonylfluoride
strong inhibition of 4-nitrophenylacetate hydrolysis
Triton X-100
strong inhibition of 4-nitrophenylacetate hydrolysis
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.001506
2-[(2,3-dihydro-4H-1,4-benzoxazine-4-carbonyl)oxy]-7-[(6-phenoxypyridin-3-yl)methyl]tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione
Homo sapiens
IC50 value is determined by competitive gel-based activity-based protein profiling, pH and temperature not specified in the publication
0.01
7-(4-chlorobenzoyl)-2-[(2,3-dihydro-4H-1,4-benzoxazine-4-carbonyl)oxy]tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione
Homo sapiens
above 0.01 mM, IC50 value is determined by competitive gel-based activity-based protein profiling, pH and temperature not specified in the publication
0.000013
7-(4-chlorobenzyl)-1,3-dioxohexahydroimidazo[1,5-a]pyrazin-2(3H)-yl 2,3-dihydro-4Hbenzo[b][1,4]oxazine-4-carboxylate
Homo sapiens
pH and temperature not specified in the publication
0.0002
7-[(2-chlorophenyl)methyl]-2-([4-(4-methoxyphenyl)piperazine-1-carbonyl]oxy)tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione
Homo sapiens
IC50 value is determined by competitive gel-based activity-based protein profiling, pH and temperature not specified in the publication
0.01
7-[(3-chlorophenyl)methyl]-2-([4-(4-methoxyphenyl)piperazine-1-carbonyl]oxy)tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione
Homo sapiens
above 0.01 mM, IC50 value is determined by competitive gel-based activity-based protein profiling, pH and temperature not specified in the publication
0.000677
7-[(4-bromophenyl)methyl]-2-[[4-(4-methoxyphenyl)piperazine-1-carbonyl]oxy]tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione
Homo sapiens
IC50 value is determined by competitive gel-based activity-based protein profiling, pH and temperature not specified in the publication
0.00029
7-[(4-chlorophenyl)methyl]-2-([4-(4-methoxyphenyl)piperazine-1-carbonyl]oxy)tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione
Homo sapiens
IC50 value is determined by competitive gel-based activity-based protein profiling, pH and temperature not specified in the publication
0.000013
7-[(4-chlorophenyl)methyl]-2-[(2,3-dihydro-4H-1,4-benzoxazine-4-carbonyl)oxy]tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione
Homo sapiens
IC50 value is determined by competitive gel-based activity-based protein profiling, pH and temperature not specified in the publication
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
the enzyme removes the palmitoleate modification that is introduced to specific L-serine residues in Wnt proteins by [Wnt protein]-O-palmitoleoyl transferase
physiological function
Notum requires glypicans to suppress Wnt signalling, but does not cleave their glycophosphatidylinositol anchor. Glycosaminoglycan binding sites on Notum probably help to co-localize with Wnt proteins. A large hydrophobic pocket at the active site accommodates palmitoleate
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
NOTUM_HUMAN
496
0
55699
Swiss-Prot
Secretory Pathway (Reliability: 4)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
54000
calculated from sequence
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
nine crystal forms at resolutions between 1.4 and 2.8 A. The catalytic triad comprises Ser232, Asp340 and His389
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
NOTUM inhibitors have potential for treating degenerative diseases
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kakugawa, S.; Langton, P.F.; Zebisch, M.; Howell, S.A.; Chang, T.H.; Liu, Y.; Feizi, T.; Bineva, G.; OReilly, N.; Snijders, A.P.; Jones, E.Y.; Vincent, J.P.
Notum deacylates Wnt proteins to suppress signalling activity
Nature
519
187-192
2015
Homo sapiens (Q6P988), Homo sapiens, Drosophila melanogaster (Q9VUX3)
Manually annotated by BRENDA team
Suciu, R.M.; Cognetta, A.B.; Potter, Z.E.; Cravatt, B.F.
Selective irreversible inhibitors of the Wnt-deacylating enzyme NOTUM developed by activity-based protein profiling
ACS Med. Chem. Lett.
9
563-568
2018
Homo sapiens, Homo sapiens (Q6P988)
Manually annotated by BRENDA team