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Information on EC 3.5.1.89 - N-acetylglucosaminylphosphatidylinositol deacetylase
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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.
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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, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2-acetamido-2-deoxy-alpha-D-glucopyranosyl-(1->6)-phosphatidylinositol de-N-acetylase
-
-
Acetylglucosaminylphosphatidylinositol deacetylase
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-
-
-
CaGpi12
Deacetylase, acetylglucosaminylphosphatidylinositol
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-
-
-
EC 3.1.1.69
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-
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
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-
-
-
N-Acetylglucosaminylphosphatidylinositol de-N-acetylase
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-
-
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N-Acetylglucosaminylphosphatidylinositol de-N-acetylase
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-
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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
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-
-
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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
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of carboxylic ester
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-
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-
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PATHWAY SOURCE
PATHWAYS
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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.
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CAS REGISTRY NUMBER
COMMENTARY
122191-30-4
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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
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-
-
-
?
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
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-
-
-
?
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
?
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-
-
-
?
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
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-
?
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
D-Glucosaminylphosphatidylinositol + acetate
N-acetyl-D-glucosaminylphosphatidylinositol + H2O + H2O
D-glucosaminylphosphatidylinositol + acetate
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-
-
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?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
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-
-
?
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
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-
?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
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?
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
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?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
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?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
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-
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?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
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?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
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?
6-(N-acetyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + acetate
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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
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-
?
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
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?
6-(N-butanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + butanoate
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very poor substrate
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?
6-(N-butanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + butanoate
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-
-
?
6-(N-hexanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + hexanoate
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-
-
?
6-(N-hexanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + hexanoate
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-
-
?
6-(N-isobutanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + isobutanoate
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poor substrate
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?
6-(N-isobutanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + isobutanoate
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-
-
?
6-(N-pentanoyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + pentanoate
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-
-
?
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
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-
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?
6-(N-propionyl-alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O
6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + propionate
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-
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?
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
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-
?
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
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synthetic substrate
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-
?
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
D-Glucosaminylphosphatidylinositol + acetate
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-
-
-
?
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
D-Glucosaminylphosphatidylinositol + acetate
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-
-
-
?
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
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-
?
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
D-Glucosaminylphosphatidylinositol + acetate
37°C
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-
?
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
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-
?
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
D-Glucosaminylphosphatidylinositol + acetate
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-
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?
N-Acetyl-D-glucosaminylphosphatidylinositol + H2O
D-Glucosaminylphosphatidylinositol + acetate
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analogues lacking the glycerophosphate component are not recognized
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?
additional information
?
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the enzyme shows an overall low activity
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-
-
additional information
?
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the enzyme shows an overall low activity
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-
-
additional information
?
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no substrate: mannosylated N-acetyl-D-glucosylphosphatidylinositol-derivatives
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?
additional information
?
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structural requirements of substrate, enzyme cannot act on analogues containing N-benzoyl-, N-acetyl-D-galactosyl- or N-acetyl-beta-D-glucosyl-groups
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?
additional information
?
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-
structural requirements of substrate, enzyme cannot act on substrate analogues containing N-acetyl-beta-glucosyl-groups or aromatic N-acyl groups
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?
additional information
?
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structural requirements of substrate, enzyme can act on analogues containing N-benzoyl-, N-acetyl-D-galactosyl- or N-acetyl-beta-D-glucosyl-groups
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?
additional information
?
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structural requirements of substrate, enzyme can act on substrate analogues containing N-acetyl-beta-glucosyl-groups or aromatic N-acyl groups
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?
additional information
?
-
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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
-
-
?
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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
-
-
?
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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
-
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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
-
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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.
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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
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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
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
the enzyme sequence contains three short hydrophobic transmembrane stretches, one at the N-terminus and two at the C-terminus
brenda
-
the enzyme sequence contains three short hydrophobic transmembrane stretches, one at the N-terminus and two at the C-terminus
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the predicted active site residues of the GPI domain are ultra-conserved for the Trypanosomatidae family. Structure comparions at the primary, secondary and tertiary level by alignment
malfunction
metabolism
physiological function
additional information
malfunction
an in vitro study using murine MQ cell line J774 shows that by the use of recombinant parasites the entry rate and infecting ability is decreased. The mutant parasites are unable to produce skin lesions even six months post-infection in the BALB/c mice
malfunction
loss of the enzyme causes reduction of GlcNAc-PI de-N-acetylase activity, cell wall defects, and filamentation defects. The filamentation defects can be specifically correlated to an upregulation of the HOG1 pathway. In the CaGPI12 conditional null strain grown under repressive conditions, no pseudohyphae or hyphae formation is observed and all cells are in the yeast form in contrast to wild-type. The CaGPI12 conditional null mutant is resistant to azoles. Reintroduction of CaGPI12 in the CaGPI12 conditional null can reverse its growth defect and restore de-N-acetylase activity
malfunction
-
loss of the enzyme causes reduction of GlcNAc-PI de-N-acetylase activity, cell wall defects, and filamentation defects. The filamentation defects can be specifically correlated to an upregulation of the HOG1 pathway. In the CaGPI12 conditional null strain grown under repressive conditions, no pseudohyphae or hyphae formation is observed and all cells are in the yeast form in contrast to wild-type. The CaGPI12 conditional null mutant is resistant to azoles. Reintroduction of CaGPI12 in the CaGPI12 conditional null can reverse its growth defect and restore de-N-acetylase activity
-
malfunction
-
an in vitro study using murine MQ cell line J774 shows that by the use of recombinant parasites the entry rate and infecting ability is decreased. The mutant parasites are unable to produce skin lesions even six months post-infection in the BALB/c mice
-
malfunction
-
an in vitro study using murine MQ cell line J774 shows that by the use of recombinant parasites the entry rate and infecting ability is decreased. The mutant parasites are unable to produce skin lesions even six months post-infection in the BALB/c mice
-
malfunction
-
an in vitro study using murine MQ cell line J774 shows that by the use of recombinant parasites the entry rate and infecting ability is decreased. The mutant parasites are unable to produce skin lesions even six months post-infection in the BALB/c mice
-
malfunction
Leishmania major MRHO
-
an in vitro study using murine MQ cell line J774 shows that by the use of recombinant parasites the entry rate and infecting ability is decreased. The mutant parasites are unable to produce skin lesions even six months post-infection in the BALB/c mice
-
metabolism
the enzyme functions at the second step of GPI anchor biosynthesis, converting N-acetylglucosaminylphosphatidylinositol to glucosaminylphosphatidylinositol. This step is conserved in the GPI biosynthesis pathway
metabolism
-
the enzyme is responsible for the second step in the glycosylphosphatidylinositol biosynthetic pathway of Trypanosoma brucei, which is a prerequisite for all subsequent steps in the pathway
metabolism
the enzyme catalyses the second step of glycosylphosphatidylinositol biosynthesis in Candida albicans
metabolism
the enzyme catalyses the second step of glycosylphosphatidylinositol biosynthesis in Trypanosoma brucei
metabolism
-
the enzyme catalyses the second step of glycosylphosphatidylinositol biosynthesis in Candida albicans
-
physiological function
Candida albicans N-acetylglucosaminylphosphatidylinositol de-N-acetylase (CaGpi12) recognises N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI) from Saccharomyces cerevisiae and is able to complement the Saccharomyces cerevisiae ScGPI12 function. CaGPI12 is able to rescue the growth defect of the ScGPI12 conditional null strain as compared to the control strain carrying the YepHIS vector alone, suggesting that CaGPI12 functionally complements ScGPI12. CaGPI12 is essential for growth and viability of Candida albicans. CaGPI12 is required for yeast to hyphal transition in Candida albicans
physiological function
GPI12 is not an essential gene for the growth and survival of Leishmania and the homozygous knockouts of Leishmania are able to survive. Stationary phase promastigotes are used for in vitro cell line J774 macrophage infectivity test also for in vivo infection
physiological function
Trypanosoma brucei is a protozoan that causes African sleeping sickness in humans. Many glycoconjugate compounds are present on the entire cell surface of Trypanosoma brucei to control the infectivity and survival of this pathogen. These glycoconjugates are anchored to the plasma membrane with the help of glycosyl phosphatidyl inositol (GPI) anchors. This type of anchor is much more common in protozoans than in other eukaryotes. The second step of glycosyl phosphatidyl inositol (GPI) anchor biosynthesis is catalyzed by an enzyme, which is GlcNAc-PI de-N-acetylase. GlcNAc-PI de-N-acetylase has a conserved GPI domain, which is responsible for the functionality of this enzyme
physiological function
-
Candida albicans N-acetylglucosaminylphosphatidylinositol de-N-acetylase (CaGpi12) recognises N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI) from Saccharomyces cerevisiae and is able to complement the Saccharomyces cerevisiae ScGPI12 function. CaGPI12 is able to rescue the growth defect of the ScGPI12 conditional null strain as compared to the control strain carrying the YepHIS vector alone, suggesting that CaGPI12 functionally complements ScGPI12. CaGPI12 is essential for growth and viability of Candida albicans. CaGPI12 is required for yeast to hyphal transition in Candida albicans
-
physiological function
-
GPI12 is not an essential gene for the growth and survival of Leishmania and the homozygous knockouts of Leishmania are able to survive. Stationary phase promastigotes are used for in vitro cell line J774 macrophage infectivity test also for in vivo infection
-
physiological function
-
GPI12 is not an essential gene for the growth and survival of Leishmania and the homozygous knockouts of Leishmania are able to survive. Stationary phase promastigotes are used for in vitro cell line J774 macrophage infectivity test also for in vivo infection
-
physiological function
-
GPI12 is not an essential gene for the growth and survival of Leishmania and the homozygous knockouts of Leishmania are able to survive. Stationary phase promastigotes are used for in vitro cell line J774 macrophage infectivity test also for in vivo infection
-
physiological function
Leishmania major MRHO
-
GPI12 is not an essential gene for the growth and survival of Leishmania and the homozygous knockouts of Leishmania are able to survive. Stationary phase promastigotes are used for in vitro cell line J774 macrophage infectivity test also for in vivo infection
-
additional information
residues Asp46 and His140 of the enzyme are important for catalysis
additional information
-
residues Asp46 and His140 of the enzyme are important for catalysis
additional information
GlcNAc-PI de-N-acetylase has a conserved GPI domain, which is responsible for the functionality of this enzyme, three-dimensional enzyme structure modeling and ligand modelling, overview. The predicted active site residues are His41, Pro42, Asp43, Asp44, Met47, Phe48, Ser74, Arg80, His103, Val144, Ser145, His147 and His150. Two hydrogen bond acceptors and four hydrogen bond donors are found in the modelled pharmacophore
additional information
-
GlcNAc-PI de-N-acetylase has a conserved GPI domain, which is responsible for the functionality of this enzyme, three-dimensional enzyme structure modeling and ligand modelling, overview. The predicted active site residues are His41, Pro42, Asp43, Asp44, Met47, Phe48, Ser74, Arg80, His103, Val144, Ser145, His147 and His150. Two hydrogen bond acceptors and four hydrogen bond donors are found in the modelled pharmacophore
additional information
two conserved motifs, HPDDE and HXXH, are both important for the enzyme function in the cell. Enzyme structure comparison of CaGPI12 with Saccharomyces cerevisiae GPI12
additional information
-
two conserved motifs, HPDDE and HXXH, are both important for the enzyme function in the cell. Enzyme structure comparison of CaGPI12 with Saccharomyces cerevisiae GPI12
additional information
-
two conserved motifs, HPDDE and HXXH, are both important for the enzyme function in the cell. Enzyme structure comparison of CaGPI12 with Saccharomyces cerevisiae GPI12
-
Show AA Sequence and Transmembrane Helices (4581 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
domain determination and protein structure homology modelling using ten templates by different threading programs
additional information
-
domain determination and protein structure homology modelling using ten templates by different threading programs
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D102A
site-directed mutagenesis of the isolated cytoplasmic catalytic domain, the mutant is active in absence of metal ions, but well stimulated by metal ions
D133A
site-directed mutagenesis of the isolated cytoplasmic catalytic domain, the mutant is active in absence of metal ions, but well stimulated by metal ions
D45A
site-directed mutagenesis of the isolated cytoplasmic catalytic domain, the mutant is active in absence of metal ions, but well stimulated by metal ions
D46A
site-directed mutagenesis of the isolated cytoplasmic catalytic domain, the mutant is only slightly active in absence of metal ions and not stimulated by metal ions
D47A
site-directed mutagenesis of the isolated cytoplasmic catalytic domain, the mutant is only slightly active in absence of metal ions, but well stimulated by metal ions
E79A
site-directed mutagenesis of the isolated cytoplasmic catalytic domain, the mutant is active in absence of metal ions, but well stimulated by metal ions
H140A
site-directed mutagenesis of the isolated cytoplasmic catalytic domain, the mutant is only slightly active in absence of metal ions and not stimulated by metal ions
H143A
site-directed mutagenesis of the isolated cytoplasmic catalytic domain, the mutant is only slightly active in absence of metal ions, but well stimulated by metal ions
H43A
site-directed mutagenesis of the isolated cytoplasmic catalytic domain, the mutant is only slightly active in absence of metal ions, but well stimulated by metal ions
additional information
additional information
a CaGPI12 heterozygous is generated by disrupting one allele with HIS1 by a PCR-mediated approach using CaGPI12-HIS1 FP and CaGPI12-HIS1 RP by the lithium-acetate (LiAc) method. The CaGPI12 conditional null mutant is made by replacing its native promoter with MET3 promoter by using the pMET3-GFP-URA3 cassette. CaGPI12 is able to rescue the growth defect of the ScGPI12 conditional null strain as compared to the control strain carrying the YepHIS vector alone, suggesting that CaGPI12 functionally complements ScGPI12. Phenotype CaGPI12 and ScGPI12 conditional null strains, overview
additional information
-
a CaGPI12 heterozygous is generated by disrupting one allele with HIS1 by a PCR-mediated approach using CaGPI12-HIS1 FP and CaGPI12-HIS1 RP by the lithium-acetate (LiAc) method. The CaGPI12 conditional null mutant is made by replacing its native promoter with MET3 promoter by using the pMET3-GFP-URA3 cassette. CaGPI12 is able to rescue the growth defect of the ScGPI12 conditional null strain as compared to the control strain carrying the YepHIS vector alone, suggesting that CaGPI12 functionally complements ScGPI12. Phenotype CaGPI12 and ScGPI12 conditional null strains, overview
additional information
-
a CaGPI12 heterozygous is generated by disrupting one allele with HIS1 by a PCR-mediated approach using CaGPI12-HIS1 FP and CaGPI12-HIS1 RP by the lithium-acetate (LiAc) method. The CaGPI12 conditional null mutant is made by replacing its native promoter with MET3 promoter by using the pMET3-GFP-URA3 cassette. CaGPI12 is able to rescue the growth defect of the ScGPI12 conditional null strain as compared to the control strain carrying the YepHIS vector alone, suggesting that CaGPI12 functionally complements ScGPI12. Phenotype CaGPI12 and ScGPI12 conditional null strains, overview
-
additional information
comparison of secondary conformation of the mutant proteins, overview
additional information
-
comparison of secondary conformation of the mutant proteins, overview
additional information
two alleles of the GPI12 gene in Leishmania major are successfully removed enabling the generation of a null mutant, which supports the idea that GPI12 is not an essential gene for the growth and survival of Leishmania and the homozygous knockouts of Leishmania are able to survive. Generation of a mutant parasite that causes no damaged to the host
additional information
-
two alleles of the GPI12 gene in Leishmania major are successfully removed enabling the generation of a null mutant, which supports the idea that GPI12 is not an essential gene for the growth and survival of Leishmania and the homozygous knockouts of Leishmania are able to survive. Generation of a mutant parasite that causes no damaged to the host
additional information
-
two alleles of the GPI12 gene in Leishmania major are successfully removed enabling the generation of a null mutant, which supports the idea that GPI12 is not an essential gene for the growth and survival of Leishmania and the homozygous knockouts of Leishmania are able to survive. Generation of a mutant parasite that causes no damaged to the host
-
additional information
-
two alleles of the GPI12 gene in Leishmania major are successfully removed enabling the generation of a null mutant, which supports the idea that GPI12 is not an essential gene for the growth and survival of Leishmania and the homozygous knockouts of Leishmania are able to survive. Generation of a mutant parasite that causes no damaged to the host
-
additional information
-
two alleles of the GPI12 gene in Leishmania major are successfully removed enabling the generation of a null mutant, which supports the idea that GPI12 is not an essential gene for the growth and survival of Leishmania and the homozygous knockouts of Leishmania are able to survive. Generation of a mutant parasite that causes no damaged to the host
-
additional information
Leishmania major MRHO
-
two alleles of the GPI12 gene in Leishmania major are successfully removed enabling the generation of a null mutant, which supports the idea that GPI12 is not an essential gene for the growth and survival of Leishmania and the homozygous knockouts of Leishmania are able to survive. Generation of a mutant parasite that causes no damaged to the host
-
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
Highly purified preparation is extremely labile, even when stored in 50% glycerol
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant N-terminally wild-type and mutant MBP-tagged cytoplasmic catalytic domains from Escherichia coli strain TB1 by amylose affinity chromatography and removal of the tag, although the MBP tag does not significantly alter the activity of the enzyme
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene GPI12, cloning in Escherichia coli strain Top 10 and tranformation and recombinant expression in Leishmaia major null mutant cells
recombinant expression of the GST-tagged enzyme in CHO MS2S cells that are defective de-N-acetylase and express the GPI anchored human CD55
-
recombinant expression of wild-type and mutant N-terminally MBP-tagged cytoplasmic catalytic domains in Escherichia coli strain TB1
the cytoplasmic domain MBPEhDELTATMPIG-L is expressed in Escherichia coli
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
the enzyme is a target in the treatment of African sleeping sickness
medicine
medicine
-
comparison of substrate specificity of human and parasite enzyme
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Doering, T.L.; Masterson, W.J.; Englund, P.T.; Hart, G.W.
Biosynthesis of the glycosyl phosphatidylinositol membrane anchor of the trypanosome variant surface glycoprotein. Origin of the non-acetylated glucosamine
J. Biol. Chem.
264
11168-11173
1989
Trypanosoma sp.
brenda
Milne, K.G.; Field, R.A.; Masterson, W.J.; Cooaz, S.; Brimacombe, J.S.; Ferguson, M.A.J.
Partial purification and characterization of the N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase of glycosylphosphatidylinositol anchor biosynthesis in African trypanosomes
J. Biol. Chem.
269
16403-16408
1994
Trypanosoma sp.
brenda
Sharma, D.K.; Smith, T.K.; Crossman, A.; Brimacombe, J.S.; Ferguson, M.A.J.
Substrate specificity of the N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase of glycosylphosphatidylinositol membrane anchor biosynthesis in African trypanosomes and human cells
Biochem. J.
328
171-177
1997
Homo sapiens, Trypanosoma brucei
brenda
Smith, T.K.; Crossman, A.; Borissow, C.N.; Paterson, M.J.; Dix, A.; Brimacombe, J.S.; Ferguson, M.A.J.
Specificity of GlcNAc-PI de-N-acetylase of GPI biosynthesis and synthesis of parasite-specific suicide substrate inhibitors
EMBO J.
20
3322-3332
2001
Homo sapiens, Trypanosoma brucei
brenda
Smith, T.K.; Crossman, A.; Paterson, M.J.; Borissow, C.N.; Brimacombe, J.S.; Ferguson, M.A.J.
Specificities of enzymes of glycosylphosphatidylinositol biosynthesis in Trypanosoma brucei and HeLa Cells
J. Biol. Chem.
277
37147-37153
2002
Homo sapiens, Trypanosoma brucei
brenda
Pielsticker, L.K.; Mann, K.J.; Lin, W.L.; Sevlever, D.
Raft-like membrane domains contain enzymatic activities involved in the synthesis of mammalian glycosylphosphatidylinositol anchor intermediates
Biochem. Biophys. Res. Commun.
330
163-171
2005
Homo sapiens
brenda
Vats, D.; Vishwakarma, R.A.; Bhattacharya, S.; Bhattacharya, A.
Reduction of cell surface glycosylphosphatidylinositol conjugates in Entamoeba histolytica by antisense blocking of E. histolytica GlcNAc-phosphatidylinositol deacetylase expression: effect on cell proliferation, endocytosis, and adhesion to target cells
Infect. Immun.
73
8381-8392
2005
Entamoeba histolytica
brenda
Pottekat, A.; Menon, A.K.
Subcellular localization and targeting of N-acetylglucosaminyl phosphatidylinositol de-N-acetylase, the second enzyme in the glycosylphosphatidylinositol biosynthetic pathway
J. Biol. Chem.
279
15743-15751
2004
Homo sapiens (Q9Y2B2), Homo sapiens
brenda
Urbaniak, M.D.; Crossman, A.; Chang, T.; Smith, T.K.; van Aalten, D.M.; Ferguson, M.A.
The N-acetyl-D-glucosaminylphosphatidylinositol De-N-acetylase of glycosylphosphatidylinositol biosynthesis is a zinc metalloenzyme
J. Biol. Chem.
280
22831-22838
2005
Rattus norvegicus (O35790), Trypanosoma brucei (Q382X3), Trypanosoma brucei
brenda
Shams-Eldin, H.; Azzouz, N.; Niehus, S.; Smith, T.K.; Schwarz, R.T.
An efficient method to express GPI-anchor proteins in insect cells
Biochem. Biophys. Res. Commun.
365
657-663
2008
Homo sapiens
brenda
Urbaniak, M.D.; Crossman, A.; Ferguson, M.A.
Probing Trypanosoma brucei glycosylphosphatidylinositol biosynthesis using novel precursor-analogues
Chem. Biol. Drug Des.
72
127-132
2008
Trypanosoma brucei
brenda
Abdelwahab, N.Z.; Urbaniak, M.D.; Ferguson, M.A.; Crossman, A.T.
Synthesis of potential metal-binding group compounds to examine the zinc dependency of the GPI de-N-acetylase metalloenzyme in Trypanosoma brucei
Carbohydr. Res.
346
708-714
2011
Trypanosoma brucei
brenda
Abdelwahab, N.Z.; Crossman, A.T.; Sullivan, L.; Ferguson, M.A.; Urbaniak, M.D.
Inhibitors incorporating zinc-binding groups target the GlcNAc-PI de-N-acetylase in Trypanosoma brucei, the causative agent of African sleeping sickness
Chem. Biol. Drug Des.
79
270-278
2012
Trypanosoma brucei
brenda
Ashraf, M.; Yadav, B.; Perinthottathil, S.; Kumar, K.S.; Vats, D.; Muthuswami, R.; Komath, S.S.
N-Acetyl-D-glucosaminylphosphatidylinositol de-N-acetylase from Entamoeba histolytica: metal alters catalytic rates but not substrate affinity
J. Biol. Chem.
286
2543-2549
2011
Entamoeba histolytica
brenda
Urbaniak, M.D.; Capes, A.S.; Crossman, A.; ONeill, S.; Thompson, S.; Gilbert, I.H.; Ferguson, M.A.
Fragment screening reveals salicylic hydroxamic acid as an inhibitor of Trypanosoma brucei GPI GlcNAc-PI de-N-acetylase
Carbohydr. Res.
387
54-58
2014
Trypanosoma brucei, Trypanosoma brucei MITat1.4
brenda
Ashraf, M.; Sreejith, P.; Yadav, U.; Komath, S.S.
Catalysis by N-acetyl-D-glucosaminylphosphatidylinositol de-N-acetylase (PIG-L) from Entamoeba histolytica: new roles for conserved residues
J. Biol. Chem.
288
7590-7595
2013
Entamoeba histolytica (C4M0W5), Entamoeba histolytica
brenda
Capes, A.S.; Crossman, A.; Urbaniak, M.D.; Gilbert, S.H.; Ferguson, M.A.; Gilbert, I.H.
Probing the substrate specificity of Trypanosoma brucei GlcNAc-PI de-N-acetylase with synthetic substrate analogues
Org. Biomol. Chem.
12
1919-1934
2014
Trypanosoma brucei
brenda
Almani, P.G.N.; Sharifi, I.; Kazemi, B.; Babaei, Z.; Bandehpour, M.; Salari, S.; Dezaki, E.S.; Tohidi, F.; Mohammadi, M.A.
The role of GlcNAc-PI-de-N-acetylase gene by gene knockout throughhomologous recombination and its consequences on survival, growthand infectivity of Leishmania major in in vitro and in vivo conditions
Acta Trop.
154
63-72
2016
Leishmania major (Q8I8A4), Leishmania major, Leishmania major 75 (Q8I8A4), Leishmania major IR (Q8I8A4), Leishmania major ER (Q8I8A4), Leishmania major MRHO (Q8I8A4)
brenda
Rashmi, M.; Swati, D.
In silico drug re-purposing against African sleeping sickness using GlcNAc-PI de-N-acetylase as an experimental target
Comput. Biol. Chem.
59
87-94
2015
Trypanosoma brucei (Q8I8A5), Trypanosoma brucei
brenda
Yadav, U.; Rai, K.T.; Sethi, S.C.; Chandraker, A.; Khan, M.A.; Komath, S.S.
Characterising N-acetylglucosaminylphosphatidylinositol de-N-acetylase (CaGpi12), the enzyme that catalyses the second step of GPI biosynthesis in Candida albicans
FEMS Yeast Res.
18
foy067
2018
Candida albicans (A0A1D8PEU2), Candida albicans, Candida albicans ATCC MYA-2876 (A0A1D8PEU2)
brenda
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