ArticleThe EMBO journal2001
Specificity of GlcNAc-PI de-N-acetylase of GPI biosynthesis and synthesis of parasite-specific suicide substrate inhibitors.
Article in The EMBO journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 53 citations in OpenAlex.
- Modulation of azole sensitivity and filamentation by GPI15, encoding a subunit of the first GPI biosynthetic enzyme, in Candida albicans.Scientific reports · 2019Article
- GlcNAc De-Applied and environmental microbiology · 2019Article
- Targeting the GPI biosynthetic pathway.Pathogens and global health · 2018Review
- Fragment screening reveals salicylic hydroxamic acid as an inhibitor of Trypanosoma brucei GPI GlcNAc-PI de-N-acetylase.Carbohydrate research · 2014Article
- Probing the substrate specificity of Trypanosoma brucei GlcNAc-PI de-N-acetylase with synthetic substrate analogues.Organic & biomolecular chemistry · 2014Article
- Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway.PLoS neglected tropical diseases · 2013Article
- Inhibitors incorporating zinc-binding groups target the GlcNAc-PI de-N-acetylase in Trypanosoma brucei, the causative agent of African sleeping sickness.Chemical biology & drug design · 2012Article
- Synthesis of potential metal-binding group compounds to examine the zinc dependency of the GPI de-N-acetylase metalloenzyme in Trypanosoma brucei.Carbohydrate research · 2011Article
- N-acetyl-D-glucosaminylphosphatidylinositol de-N-acetylase from Entamoeba histolytica: metal alters catalytic rates but not substrate affinity.The Journal of biological chemistry · 2011Article
- Lipid metabolism in Trypanosoma brucei.Molecular and biochemical parasitology · 2010Review
- Drug targets in Leishmania.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2010Article
- Trypanosome glycosylphosphatidylinositol biosynthesis.The Korean journal of parasitology · 2009Review
- Chemical validation of GPI biosynthesis as a drug target against African sleeping sickness.The EMBO journal · 2004Article
- Secretory pathway of trypanosomatid parasites.Microbiology and molecular biology reviews : MMBR · 2002Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The substrate specificities of Trypanosoma brucei and human (HeLa) GlcNAc-PI de-N-acetylases were determined using 24 substrate analogues. The results show the following. (i) The de-N-acetylases show little specificity for the lipid moiety of GlcNAc-PI. (ii) The 3'-OH group of the GlcNAc residue is essential for substrate recognition whereas the 6'-OH group is dispensable and the 4'-OH, while not required for recognition, cannot be epimerized or substituted. (iii) The parasite enzyme can act on analogues containing betaGlcNAc or aromatic N-acyl groups, whereas the human enzyme cannot. (iv) Three GlcNR-PI analogues are de-N-acetylase inhibitors, one of which is a suicide inhibitor. (v) The suicide inhibitor most likely forms a carbamate or thiocarbamate ester to an active site hydroxy-amino acid or Cys or residue such that inhibition is reversed by certain nucleophiles. These and previous results were used to design two potent (IC50 = 8 nM) parasite-specific suicide substrate inhibitors. These are potential lead compounds for the development of anti-protozoan parasite drugs.
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