Any feedback?
Information on EC 3.5.1.89 - N-acetylglucosaminylphosphatidylinositol deacetylase
for references in articles please use BRENDA:EC3.5.1.89Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
3.5.1.89 N-acetylglucosaminylphosphatidylinositol deacetylaseIUBMB Comments
Involved in the second step of glycosylphosphatidylinositol (GPI) anchor formation in all eukaryotes. The enzyme appears to be composed of a single subunit (PIG-L in mammalian cells and GPI12 in yeast). In some species, the long-chain sn-1-acyl group of the phosphatidyl group is replaced by a long-chain alkyl or alk-1-enyl group.
Specify your search results
Word Map
- 3.5.1.89
- glycosylphosphatidylinositol
-
trypanosomal
-
glcn-pi
- sickness
-
gpi-anchored
-
de-n-acetylation
- alpha-mannosyltransferase
- medicine
-
mannosylated
- drug development
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
Synonyms
glcnac-pi de-n-acetylase, pig-l, gpi12, tbgpi12, cagpi12, pig-l protein, denac, n-acetylglucosaminylphosphatidylinositol deacetylase, glcnac-pi-de-n-acetylase, n-acetylglucosaminylphosphatidylinositol de-n-acetylase, 
more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2-acetamido-2-deoxy-alpha-D-glucopyranosyl-(1->6)-phosphatidylinositol de-N-acetylase
-
-
Acetylglucosaminylphosphatidylinositol deacetylase
-
-
-
-
CaGpi12
Deacetylase, acetylglucosaminylphosphatidylinositol
-
-
-
-
EC 3.1.1.69
-
-
formerly
-
GlcNAc-phosphatidylinositol deacetylase
GlcNAc-PI de-N-acetylase
GlcNAc-PI deacetylase
GlcNAc-PI-de-N-acetylase
GPI
GPI12
N-acetyl-D-glucosaminylphosphatidylinositol de-N-acetylase
N-acetylglucosaminyl phosphatidylinositol de-N-acetylase
N-Acetylglucosaminylphosphatidylinositol de-N-acetylase
TbGPI12
GlcNAc-PI deacetylase
-
-
-
-
N-Acetylglucosaminylphosphatidylinositol de-N-acetylase
-
-
-
-
N-Acetylglucosaminylphosphatidylinositol de-N-acetylase
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O = 6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O = 6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
-
-
-
-
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O = 6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
a general acid-base pair catalytic mechanism that involves enzyme residues Asp46 and His140
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of carboxylic ester
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PATHWAY SOURCE
PATHWAYS
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYSTEMATIC NAME
IUBMB Comments
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol acetylhydrolase
Involved in the second step of glycosylphosphatidylinositol (GPI) anchor formation in all eukaryotes. The enzyme appears to be composed of a single subunit (PIG-L in mammalian cells and GPI12 in yeast). In some species, the long-chain sn-1-acyl group of the phosphatidyl group is replaced by a long-chain alkyl or alk-1-enyl group.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
122191-30-4
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
(1R,2R)-1-O-(2-acetylamino-2-deoxy-alpha-D-glucopyranosyl)-cyclohexanediol 2-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate) + H2O
?
-
-
-
-
?
1-D-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 1-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate) + H2O
?
-
-
-
-
?
2-acetamido-2-deoxy-alpha-D-glucopyranosyl-(1->6)-phosphatidylinositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
-
-
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
6-(N-butanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + butanoate
6-(N-hexanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + hexanoate
6-(N-isobutanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + isobutanoate
6-(N-pentanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + pentanoate
6-(N-propionyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + propionate
D-GlcNAc-alpha(1->6)-D-myo-inositol-1-octadecyl phosphate + H2O
D-GlcN-alpha(1->6)-D-myo-inositol-1-octadecyl phosphate + acetate
-
-
-
-
?
D-GlcNAc-alpha1-6-D-myo-inositol-1-HPO4-3-sn-1,2-diacylglycerol + H2O
?
-
-
-
-
?
N,N-diethylethanaminium 1-D-2-[(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)oxy]-myo-inosityl octadecyl phosphate + H2O
?
-
-
-
-
?
N-acetyl-D-glucosamine-alpha-(1-6)-D-myo-inositol-1-octadecyl phosphate + H2O
D-glucosamine-alpha-(1-6)-D-myo-inositol-1-octadecyl phosphate + acetate
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
?
-
involved in the formation of the glycosylphosphatidylinositol membrane anchor of the trypanosome variant-surface glycoprotein
-
-
?
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
D-Glucosaminylphosphatidylinositol + acetate
N-acetyl-D-glucosaminylphosphatidylinositol + H2O + H2O
D-glucosaminylphosphatidylinositol + acetate
-
-
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
-
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
the substrate is prepared from Saccharomyces cerevisiae microsomes. [6-3H]GlcN-PI is converted to [6-3H]GlcNAc-PI using anhydride
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
-
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
the substrate is prepared from Saccharomyces cerevisiae microsomes. [6-3H]GlcN-PI is converted to [6-3H]GlcNAc-PI using anhydride
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
-
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
-
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
-
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
-
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
-
the phosphate, 2'-NHAc and 3'-OH groups of the natural substrate alpha-D-GlcpNAc-PI are critical for recognition by the Trypanosoma brucei GlcNAc-PI de-N-acetylase
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
substrate binding analysis by docking with Zn2+ to the enzyme's active site
-
-
?
6-(N-butanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + butanoate
-
very poor substrate
-
?
6-(N-butanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + butanoate
-
-
-
?
6-(N-hexanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + hexanoate
-
-
-
?
6-(N-hexanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + hexanoate
-
-
-
?
6-(N-isobutanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + isobutanoate
-
poor substrate
-
?
6-(N-isobutanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + isobutanoate
-
-
-
?
6-(N-pentanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + pentanoate
-
-
-
?
6-(N-pentanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + pentanoate
-
-
-
?
6-(N-propionyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + propionate
-
-
-
?
6-(N-propionyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + propionate
-
-
-
?
N-acetyl-D-glucosamine-alpha-(1-6)-D-myo-inositol-1-octadecyl phosphate + H2O
D-glucosamine-alpha-(1-6)-D-myo-inositol-1-octadecyl phosphate + acetate
-
synthetic substrate
-
-
?
N-acetyl-D-glucosamine-alpha-(1-6)-D-myo-inositol-1-octadecyl phosphate + H2O
D-glucosamine-alpha-(1-6)-D-myo-inositol-1-octadecyl phosphate + acetate
-
synthetic substrate
-
-
?
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
D-Glucosaminylphosphatidylinositol + acetate
-
-
-
-
?
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
D-Glucosaminylphosphatidylinositol + acetate
-
-
-
-
?
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
D-Glucosaminylphosphatidylinositol + acetate
37°C, pH 7.4, 25 mM KCl, 5 mM MgCl2, 5 mM MnCl2, 0.5 mM dithiothreitol, 0.1 mM 1-chloro-3-tosylamido-7-amino-2-heptanone, 1 microg/ml leupeptin
-
-
?
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
D-Glucosaminylphosphatidylinositol + acetate
37°C
-
-
?
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
D-Glucosaminylphosphatidylinositol + acetate
30°C, pH 7.4, 50 mM KCl, 10 mM dithiothreitol, 0.1 mM 1-chloro-3-tosylamido-7-amino-2-heptanone, 1 microg/ml leupeptin
-
-
?
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
D-Glucosaminylphosphatidylinositol + acetate
-
-
-
?
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
D-Glucosaminylphosphatidylinositol + acetate
-
analogues lacking the glycerophosphate component are not recognized
-
?
additional information
?
-
the enzyme shows an overall low activity
-
-
-
additional information
?
-
the enzyme shows an overall low activity
-
-
-
additional information
?
-
-
no substrate: mannosylated N-acetyl-D-glucosylphosphatidylinositol-derivatives
-
?
additional information
?
-
-
structural requirements of substrate, enzyme cannot act on analogues containing N-benzoyl-, N-acetyl-D-galactosyl- or N-acetyl-beta-D-glucosyl-groups
-
?
additional information
?
-
-
structural requirements of substrate, enzyme cannot act on substrate analogues containing N-acetyl-beta-glucosyl-groups or aromatic N-acyl groups
-
?
additional information
?
-
-
structural requirements of substrate, enzyme can act on analogues containing N-benzoyl-, N-acetyl-D-galactosyl- or N-acetyl-beta-D-glucosyl-groups
-
?
additional information
?
-
-
structural requirements of substrate, enzyme can act on substrate analogues containing N-acetyl-beta-glucosyl-groups or aromatic N-acyl groups
-
?
additional information
?
-
-
substrate specificity in decreasing order: N-acetyl-D-glucosylphosphatidylinositol, N-propionylglucosylphosphatidylinositol, N-butyrylglucosylphosphatidylinositol, N-isobutyrylglucosylphosphatidylinositol, N-pentanoylglucosylphosphatidylinositol, N-hexanoylglucosylphosphatidylinositol, no substrate: mannosylated N-acetyl-D-glucosylphosphatidylinositol-derivatives
-
?
additional information
?
-
-
synthesis of substrate analogues and substrate structure-activity analysis, molecular dynamics simulations, overview. (1R,2R)-1-O-(2-acetylamino-2-deoxy-beta-D-glucopyranosyl)-cyclohexanediol 2-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate) is neither a substrate nor an inhibitor. No recognition and activity with substrate analogues (1R,2R)-2-[(2-amino-2-deoxy-alpha-D-glucopyranosyl)oxy]cyclohexyl octadecyl phosphate, (1R,2R)-2-[(2-amino-2-deoxy-beta-D-glucopyranosyl)oxy]cyclohexyl octadecyl phosphate, (1R,2R)-1-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-cyclohexanediol 2-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate), (1R,2R)-1-O-(2-amino-2-deoxy-beta-D-glucopyranosyl)-cyclohexanediol 2-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate), N-(1R,2R)-2-O-(2-amino-2-deoxy-beta-D-glucopyranosyl)-cyclohexyloctadecane-1-sulphonamide, N-(1R,2R)-2-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-cyclohexyloctadecane-1-sulphonamide, and triethylammonium trans-2-(2-amino-3-hydroxypropoxy)-cyclohexyl n-octadecyl phosphate, as well as with (1R,2R)-2-[(2-acetylamino-2-deoxy-alpha-D-glucopyranosyl)oxy]cyclohexyl octadecyl phosphate, (1R,2R)-2-[(2-acetamido-2-deoxy-beta-D-glucopyranosyl)oxy]cyclohexyl octadecyl phosphate, (1R,2R)-1-O-(2-acetylamino-2-deoxy-beta-D-glucopyranosyl)-cyclohexanediol 2-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate), N-((1R,2R)-2-[(2-acetamido-2-deoxy-beta-D-glucopyranosyl)oxy]cyclohexyl)octadecane-1-sulfonamide, N-((1R,2R)-2-[(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)oxy]cyclohexyl)octadecane-1-sulfonamide, and N,N-diethylethanaminium (1R,2R)-2-(2-acetamido-3-hydroxypropoxy)cyclohexyl octadecyl phosphate. The requirement for the presence of inositol 2-, 3-, 4-, and 5-OH groups for recognition by the enzyme is nuanced and may depend on the conformational flexibility of the substrate analogue. The glucosamine and the phospholipid moieties are essential for binding and, while the D-myo-inositol residue is the preferred aglycone for recognition by the enzyme, the dispensing of it entirely with a cyclohexanediol group is tolerated by the enzyme
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
2-acetamido-2-deoxy-alpha-D-glucopyranosyl-(1->6)-phosphatidylinositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
-
-
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
?
-
involved in the formation of the glycosylphosphatidylinositol membrane anchor of the trypanosome variant-surface glycoprotein
-
-
?
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
D-Glucosaminylphosphatidylinositol + acetate
-
-
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
-
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
-
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
-
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
-
-
-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
-
the phosphate, 2'-NHAc and 3'-OH groups of the natural substrate alpha-D-GlcpNAc-PI are critical for recognition by the Trypanosoma brucei GlcNAc-PI de-N-acetylase
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
Cu2+
Mg2+
Mn2+
Ni2+
Zn2+
additional information
Co2+
-
the de-N-acetylase activity of the cyctoplasmic domain MBPEhDELTATMPIG-L is 2fold higher in the presence of 5 mM Co2+
Mg2+
-
the de-N-acetylase activity of the cyctoplasmic domain MBPEhDELTATMPIG-L is 2fold higher in the presence of 5 mM Mg2+
Mn2+
-
the de-N-acetylase activity of the cyctoplasmic domain MBPEhDELTATMPIG-L is 2fold higher in the presence of 5 mM Mn2+
Mn2+
stimulates, binding of Mn2+ to the isolated cytoplasmic catalytic domain of the enzyme results in a significant alteration in the global conformation of the protein
Zn2+
required, does not activate the enzyme, a metal-dependent enzyme
additional information
a metal-dependent enzyme that is stimulated by divalent cations but shows no preference for Zn2+ unlike the mammalian homologue. It irreversibly loses activity upon incubation with a metal chelator. Fe2+ has no significant effect on the enzyme activity
additional information
-
a metal-dependent enzyme that is stimulated by divalent cations but shows no preference for Zn2+ unlike the mammalian homologue. It irreversibly loses activity upon incubation with a metal chelator. Fe2+ has no significant effect on the enzyme activity
additional information
-
5 mM Zn2+ does not stimulate the de-N-acetylase activity of the cyctoplasmic domain MBPEhDELTATMPIG-L
additional information
-
the protein is active even in the absence of metal. The metal ion does not directly participate in ligand binding or recognition but is important for the catalytic efficiency of the enzymatic site
additional information
the enzyme exhibits a novel metal-independent albeit metal-stimulated activity
additional information
-
the enzyme exhibits a novel metal-independent albeit metal-stimulated activity
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1R,2R)-1-O-(2-acetylamino-2-deoxy-alpha-D-glucopyranosyl)-cyclohexanediol 2-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate)
-
competitive
(1R,2R)-1-O-(2-acetylamino-2-deoxy-beta-D-glucopyranosyl)-cyclohexanediol 2-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate)
-
-
(1R,2R)-1-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-cyclohexanediol 2-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate)
-
-
(1R,2R)-1-O-(2-amino-2-deoxy-beta-D-glucopyranosyl)-cyclohexanediol 2-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate)
-
-
(1R,2R)-2-((2-deoxy-2-[(hydroxycarbamoyl)amino]-beta-D-glucopyranosyl)oxy)cyclohexyl octadecyl phosphate
-
-
(1R,2R)-2-[(2-acetamido-2-deoxy-beta-D-glucopyranosyl)oxy]cyclohexyl octadecyl phosphate
-
-
(1R,2R)-2-[(2-acetylamino-2-deoxy-alpha-D-glucopyranosyl)oxy]cyclohexyl octadecyl phosphate
-
-
(1R,2R)-2-[(2-amino-2-deoxy-alpha-D-glucopyranosyl)oxy]cyclohexyl octadecyl phosphate
-
-
(1R,2R)-2-[(2-amino-2-deoxy-beta-D-glucopyranosyl)oxy]cyclohexyl octadecyl phosphate
-
-
(1R,2R,3S,4R,5R,6R)-2-([2-deoxy-2-[(hydroxycarbamoyl)amino]-alpha-D-glucopyranosyl]oxy)-3,4,5,6-tetrahydroxycyclohexyl octadecyl hydrogen phosphate
-
-
(1R,2S,3R,4R,5R)-4-(prop-2-en-1-yl)-6,8-dioxabicyclo[3.2.1]octane-2,3-diyl diacetate
-
-
(2R)-3-{[{[(1R,2R,3S,4R,5R,6R)-2-{[2-(carbamoylamino)-2-deoxy-alpha-D-glucopyranosyl]oxy}-3,4,5,6-tetrahydroxycyclohexyl]oxy}(hydroxy)phosphoryl]oxy}propane-1,2-diyl dihexadecanoate
-
-
1,3,4,6-tetra-O-acetyl-2-C-carboxymethyl-2-deoxy-alpha-D-glucopyranose
-
-
1,5-anhydro-2-deoxy-2-[2-(hydroxyamino)-2-oxoethyl]-3-O-phenyl-D-glucitol
-
-
1,5-anhydro-3-O-benzyl-2-deoxy-2-[2-(hydroxyamino)-2-oxoethyl]-D-glucitol
-
-
1,5-anhydro-3-O-benzyl-4,6-O-benzylidene-2-(carboxymethyl)-2-deoxy-D-glucitol
-
-
1,5-anhydro-3-O-benzyl-4,6-O-benzylidene-2-[2-[(benzyloxy)amino]-2-oxoethyl]-2-deoxy-D-glucitol
-
-
1,5-anhydro-4,6-O-benzylidene-2-[2-[(benzyloxy)amino]-2-oxoethyl]-2-deoxy-D-glucitol
-
-
1-acetyl-N-[4-hydroxy-3-(hydroxycarbamoyl)phenyl]piperidine-4-carboxamide
-
40% inhibition at 1 mM
1-{1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}-2-hydroxyethan-1-one
-
-
2-deoxy-2-ureido-D-galactosylalpha1-6-D-myo-inositol-1-phosphoryl-sn-1,2-dipalmitoylglycerol
-
suicide inhibitor, 50% inihibition at 0.0002 mM
2-deoxy-2-ureido-D-glucosyl-alpha1-6-D-myo-inositol-1-phosphoryl-sn-1,2-dipalmitoylglycerol
2-deoxy-2-ureido-D-glucosyl-beta1-6-D-myo-inositol-1-phosphoryl-sn-1,2-dipalmitoylglycerol
-
50% inhibition at about 8 nM
2-deoxy-2-ureido-D-glucosylalpha1-6-D-(2-O-octyl)myo-inositol-1-phosphoryl-sn-1,2-dipalmitoylglycerol
-
50% inhibition at about 8 nM
2-deoxy-2-ureido-D-glucosylbeta1-6-D-myo-inositol-1-phosphoryl-sn-1,2-dipalmitoylglycerol
-
suicide inhibitor, 50% inihibition at 0.0002 mM
5-[(cyclohexanecarbonyl)amino]-N,2-dihydroxybenzamide
-
99% inhibition at 1 mM
EDTA
complete inhibition at 10 mM, the enzyme irreversibly loses activity upon incubation with a metal chelator
ethambutol
docking study, the effective enzyme inhibitor may be useful in the treatment of African sleeping sickness
metaraminol
docking study, the effective enzyme inhibitor may be useful in the treatment of African sleeping sickness
N,N-diethylethanaminium (1R,2R)-2-(2-acetamido-3-hydroxypropoxy)cyclohexyl octadecyl phosphate
-
-
N,N-diethylethanaminium 1-D-2-[(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)oxy]-myo-inosityl octadecyl phosphate
-
-
N-((1R,2R)-2-[(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)oxy]cyclohexyl)octadecane-1-sulfonamide
-
-
N-((1R,2R)-2-[(2-acetamido-2-deoxy-beta-D-glucopyranosyl)oxy]cyclohexyl)octadecane-1-sulfonamide
-
-
N-(1R,2R)-2-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-cyclohexyloctadecane-1-sulphonamide
-
-
N-(1R,2R)-2-O-(2-amino-2-deoxy-beta-D-glucopyranosyl)-cyclohexyloctadecane-1-sulphonamide
-
-
N-dimethyl-D-glucosyl-phosphatidylinositol
-
0.001 mM, complete inhibition
N-[4-hydroxy-3-(hydroxycarbamoyl)phenyl]-2H-1,3-benzodioxole-5-carboxamide
-
86% inhibition at 1 mM
N-[4-hydroxy-3-(hydroxycarbamoyl)phenyl]oxane-4-carboxamide
-
56% inhibition at 1 mM
N-[4-hydroxy-3-(hydroxycarbamoyl)phenyl][1,1'-biphenyl]-4-carboxamide
-
75% inhibition at 1 mM
phenyl 3,4,6-tri-O-acetyl-2-C-allyl-2-deoxy-1-thio-alpha-D-glucopyranoside
-
-
phenyl 3,4,6-tri-O-acetyl-2-C-allyl-2-deoxy-1-thio-beta-D-glucopyranoside
-
-
phenyl 3,4,6-tri-O-acetyl-2-C-carboxymethyl-2-deoxy-1-thio-alpha-D-glucopyranoside
-
-
phenyl 3,4,6-tri-O-acetyl-2-C-carboxymethyl-2-deoxy-1-thio-beta-D-glucopyranoside
-
-
phenyl 3,4,6-tri-O-acetyl-2-deoxy-2-C-formylmethyl-1-thio-alpha-D-glucopyranoside
-
-
phenyl 3,4,6-tri-O-acetyl-2-deoxy-2-C-formylmethyl-1-thio-beta-D-glucopyranoside
-
-
salicylic hydroxamic acid
-
enzyme inhibitor with high ligand efficiency, proposed mode of action, overview
triethylammonium 1R,2R-1-O-[2-C-(carboxymethyl N-hydroxyamide)-2-deoxy-beta-D-glucopyranosyl]-cyclohexanediol 2-(n-octadecylphosphate)
-
-
triethylammonium trans-2-(2-amino-3-hydroxypropoxy)-cyclohexyl n-octadecyl phosphate
-
-
2-deoxy-2-ureido-D-glucosyl-alpha1-6-D-myo-inositol-1-phosphoryl-sn-1,2-dipalmitoylglycerol
-
50% inhibition between 0.0001 and 0.001 mM
2-deoxy-2-ureido-D-glucosyl-alpha1-6-D-myo-inositol-1-phosphoryl-sn-1,2-dipalmitoylglycerol
-
50% inhibition at 8 nM
additional information
-
treatment with EDTA consistently causes up to 2% reduction in activity, the activity is not significantly affected by treatment with 1,10-phenanthroline
-
additional information
-
not inhibitory up to 0.1 mM: 2-deoxy-2-ureido-D-glucosyl-beta1-6-D-myo-inositol-1-phosphoryl-sn-1,2-dipalmitoylglycerol, 2-deoxy-2-ureido-D-glucosylalpha1-6-D-(2-O-octyl)myo-inositol-1-phosphoryl-sn-1,2-dipalmitoylglycerol
-
additional information
-
inhibitor identification via zinc binding fragment screening, structure activity relationship, hydroxamic acid and 2-OH are essential for potency, substitution is tolerated at the 4- and 5-positions. No inhibition by 2-bromo-N-hydroxybenzamide and 2-amino-N-hydroxybenzamide
-
additional information
-
(1R,2R)-1-O-(2-acetylamino-2-deoxy-beta-D-glucopyranosyl)-cyclohexanediol 2-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate) is neither a substrate nor an inhibitor
-
additional information
inhibitor search by structural based virtual screening (SBVS), molecular modeling, and docking study, overview
-
additional information
-
inhibitor search by structural based virtual screening (SBVS), molecular modeling, and docking study, overview
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
a tightly bound divalent metal cation is essential for activity
-
additional information
a tightly bound divalent metal cation is essential for activity
-
additional information
-
a tightly bound divalent metal cation is essential for activity
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Thymoma
Subcellular localization and targeting of N-acetylglucosaminyl phosphatidylinositol de-N-acetylase, the second enzyme in the glycosylphosphatidylinositol biosynthetic pathway.
Trypanosomiasis, African
Cloning of Trypanosoma brucei and Leishmania major genes encoding the GlcNAc-phosphatidylinositol de-N-acetylase of glycosylphosphatidylinositol biosynthesis that is essential to the African sleeping sickness parasite.
Trypanosomiasis, African
Fragment screening reveals salicylic hydroxamic acid as an inhibitor of Trypanosoma brucei GPI GlcNAc-PI de-N-acetylase.
Trypanosomiasis, African
In silico drug re-purposing against African sleeping sickness using GlcNAc-PI de-N-acetylase as an experimental target.
Trypanosomiasis, African
Inhibitors incorporating zinc-binding groups target the GlcNAc-PI de-N-acetylase in Trypanosoma brucei, the causative agent of African sleeping sickness.
Trypanosomiasis, African
The N-acetyl-D-glucosaminylphosphatidylinositol De-N-acetylase of glycosylphosphatidylinositol biosynthesis is a zinc metalloenzyme.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00137
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol
pH 5.5, 37°C, recombinant mutant H140A cytoplasmic catalytic domain, metal added
0.0016
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol
pH 5.5, 37°C, recombinant mutant H140A cytoplasmic catalytic domain, no metal added
0.00182
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol
pH 5.5, 37°C, recombinant mutant D46A cytoplasmic catalytic domain, no metal added
0.00195
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol
pH 5.5, 37°C, recombinant mutant D46A cytoplasmic catalytic domain, metal added
0.00195
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol
pH 5.5, 37°C, recombinant wild-type cytoplasmic catalytic domain, no metal added
0.00199
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol
pH 5.5, 37°C, recombinant mutant H43A cytoplasmic catalytic domain, no metal added
0.00209
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol
pH 5.5, 37°C, recombinant wild-type cytoplasmic catalytic domain, metal added
0.00263
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol
pH 5.5, 37°C, recombinant mutant H43A cytoplasmic catalytic domain, metal added
0.00195
N-acetyl-D-glucosaminylphosphatidylinositol
-
in the absence of metal ions, in 50 mM acetate buffer at pH 5.5 and 37°C
0.00205
N-acetyl-D-glucosaminylphosphatidylinositol
-
in the presence of 5 mM Mn2+, in 50 mM acetate buffer at pH 5.5 and 37°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
10
1,5-anhydro-2-(carboxymethyl)-2-deoxy-D-glucitol
Trypanosoma brucei
-
IC50 above 10 mM, in 50 mM Na-HEPES pH 7.4, 25 mM KCl, 0.1 mM Tos-LysCH2Cl and 0.001 mg/ml leupeptin, at 30°C
10
1,5-anhydro-2-deoxy-2-[2-(hydroxyamino)-2-oxoethyl]-D-glucitol
Trypanosoma brucei
-
IC50 above 10 mM, in 50 mM Na-HEPES pH 7.4, 25 mM KCl, 0.1 mM Tos-LysCH2Cl and 0.001 mg/ml leupeptin, at 30°C
0.29
1,5-anhydro-3-O-benzyl-2-(carboxymethyl)-2-deoxy-D-glucitol
Trypanosoma brucei
-
in 50 mM Na-HEPES pH 7.4, 25 mM KCl, 0.1 mM Tos-LysCH2Cl and 0.001 mg/ml leupeptin, at 30°C
1.5
1,5-anhydro-3-O-benzyl-2-deoxy-2-[2-(hydroxyamino)-2-oxoethyl]-D-glucitol
Trypanosoma brucei
-
in 50 mM Na-HEPES pH 7.4, 25 mM KCl, 0.1 mM Tos-LysCH2Cl and 0.001 mg/ml leupeptin, at 30°C
0.3
2-(carboxymethyl)-2-deoxy-D-glucopyranose
Trypanosoma brucei
-
in 50 mM Na-HEPES pH 7.4, 25 mM KCl, 0.1 mM Tos-LysCH2Cl and 0.001 mg/ml leupeptin, at 30°C
10
phenyl 2-(carbamoylamino)-2-deoxy-1-thio-beta-D-glucopyranoside
Trypanosoma brucei
-
IC50 above 10 mM, in 50 mM Na-HEPES pH 7.4, 25 mM KCl, 0.1 mM Tos-LysCH2Cl and 0.001 mg/ml leupeptin, at 30°C
0.019
triethylammonium 1R,2R-1-O-[2-C-(carboxymethyl N-hydroxyamide)-2-deoxy-beta-D-glucopyranosyl]-cyclohexanediol 2-(n-octadecylphosphate)
Trypanosoma brucei
-
in 50 mM Na-HEPES pH 7.4, 25 mM KCl, 0.1 mM Tos-LysCH2Cl and 0.001 mg/ml leupeptin, at 30°C
0.1
phenyl 2-(carboxymethyl)-2-deoxy-1-thio-alpha-D-glucopyranoside
Trypanosoma brucei
-
in 50 mM Na-HEPES pH 7.4, 25 mM KCl, 0.1 mM Tos-LysCH2Cl and 0.001 mg/ml leupeptin, at 30°C
10
phenyl 2-(carboxymethyl)-2-deoxy-1-thio-alpha-D-glucopyranoside
Trypanosoma brucei
-
IC50 above 10 mM, in 50 mM Na-HEPES pH 7.4, 25 mM KCl, 0.1 mM Tos-LysCH2Cl and 0.001 mg/ml leupeptin, at 30°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY