Literature summary for 3.5.1.89 extracted from

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 (2014), Carbohydr. Res., 387, 54-58.

Cloned(Commentary)

Cloned (Comment)	Organism
recombinant expression of the GST-tagged enzyme in CHO MS2S cells that are defective de-N-acetylase and express the GPI anchored human CD55	Trypanosoma brucei

Inhibitors

Inhibitors	Comment	Organism
1-acetyl-N-[4-hydroxy-3-(hydroxycarbamoyl)phenyl]piperidine-4-carboxamide	40% inhibition at 1 mM	Trypanosoma brucei
1-{1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}-2-hydroxyethan-1-one	-	Trypanosoma brucei
2-(2,4-dichlorophenoxy)-N-hydroxyacetamide	-	Trypanosoma brucei
2-hydroxybenzoic acid	97% inhibition at 1 mM	Trypanosoma brucei
3-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]-N-hydroxypropanamide	-	Trypanosoma brucei
4-(2,4-dichlorophenoxy)-N-hydroxybutanamide	-	Trypanosoma brucei
4-bromo-N,2-dihydroxybenzamide	86% inhibition at 1 mM	Trypanosoma brucei
4-bromo-N-hydroxybenzamide	9.6% inhibition at 1 mM	Trypanosoma brucei
5-((tert-butoxycarbonyl)amino)-2-hydroxybenzoic acid	-	Trypanosoma brucei
5-amino-N-(benzyloxy)-2-hydroxybenzamide	-	Trypanosoma brucei
5-benzamido-N,2-dihydroxybenzamide	96% inhibition at 1 mM	Trypanosoma brucei
5-[(cyclohexanecarbonyl)amino]-N,2-dihydroxybenzamide	99% inhibition at 1 mM	Trypanosoma brucei
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	Trypanosoma brucei
N,2-dihydroxy-5-(4-methylbenzamido)benzamide	62% inhibition at 1 mM	Trypanosoma brucei
N,2-dihydroxy-5-(octadecanoylamino)benzamide	25% inhibition at 1 mM	Trypanosoma brucei
N-hydroxy-N'-(4-methoxyphenyl)urea	-	Trypanosoma brucei
N-hydroxybenzamide	25% inhibition at 1 mM	Trypanosoma brucei
N-[4-hydroxy-3-(hydroxycarbamoyl)phenyl]-2H-1,3-benzodioxole-5-carboxamide	86% inhibition at 1 mM	Trypanosoma brucei
N-[4-hydroxy-3-(hydroxycarbamoyl)phenyl]oxane-4-carboxamide	56% inhibition at 1 mM	Trypanosoma brucei
N-[4-hydroxy-3-(hydroxycarbamoyl)phenyl][1,1'-biphenyl]-4-carboxamide	75% inhibition at 1 mM	Trypanosoma brucei
salicylic hydroxamic acid	enzyme inhibitor with high ligand efficiency, proposed mode of action, overview	Trypanosoma brucei
tert-butyl (3-((benzyloxy)carbamoyl)-4-hydroxyphenyl)carbamate	-	Trypanosoma brucei

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mn2+	activates	Trypanosoma brucei
Zn2+	a zinc-metalloenzyme	Trypanosoma brucei

Organism

Organism	UniProt	Comment	Textmining
Trypanosoma brucei	-	-	-
Trypanosoma brucei MITat1.4	-	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
N-acetyl-D-glucosamine-alpha-(1-6)-D-myo-inositol-1-octadecyl phosphate + H2O	synthetic substrate	Trypanosoma brucei	D-glucosamine-alpha-(1-6)-D-myo-inositol-1-octadecyl phosphate + acetate	-	?
N-acetyl-D-glucosamine-alpha-(1-6)-D-myo-inositol-1-octadecyl phosphate + H2O	synthetic substrate	Trypanosoma brucei MITat1.4	D-glucosamine-alpha-(1-6)-D-myo-inositol-1-octadecyl phosphate + acetate	-	?

Synonyms

Synonyms	Comment	Organism
GlcNAc-PI de-N-acetylase	-	Trypanosoma brucei
GPI	-	Trypanosoma brucei
TbGPI12	-	Trypanosoma brucei

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Trypanosoma brucei

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
8	-	assay at	Trypanosoma brucei

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.063	-	pH 8.0, 37°C	Trypanosoma brucei	salicylic hydroxamic acid