Abstract
In order to study the O-GlcNAc modification in vivo, it is evident that a range of specific small molecule inhibitors would be a valuable asset. One strategy for the design of such compounds would be to utilise 3-D structural information in tandem with knowledge of catalytic mechanism. The last few years has seen major breakthroughs in our understanding of the 3-D structure of the enzymes involved in the O-GlcNAc modification notably from the study of the tetratricopeptide repeat (TPR) domain of the human O-GlcNAc transferase, of the bacterial homologs of the O-GlcNAc hydrolase and more latterly bacterial homologs of the O-GlcNAc transferase itself. Of particular note are the bacterial O-GlcNAc hydrolase homologs that provide near identical active centres to the human enzyme. These have informed the design and/or subsequent analysis of inhibitors of this enzyme which have found great use in the chemical dissection of the O-GlcNAc in vivo, as described by Macauley and Vocadlo elsewhere in this issue. (C) 2009 Elsevier B.V. All rights reserved.
| Original language | English |
|---|---|
| Pages (from-to) | 122-133 |
| Number of pages | 12 |
| Journal | BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS |
| Volume | 1800 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2010 |
Keywords
- Structure
- O-GlcNAc
- Enzyme
- Reaction mechanism
- Carbohydrate-active enzyme
- GH84
- GT41
- Hydrolase
- Transferase
- BETA-N-ACETYLGLUCOSAMINIDASE
- SUBSTRATE-ASSISTED CATALYSIS
- TAY-SACHS-DISEASE
- LINKED GLCNAC
- CRYSTAL-STRUCTURE
- GLYCOSIDE HYDROLASES
- FUNCTIONAL-ANALYSIS
- NUCLEOCYTOPLASMIC PROTEINS
- TETRATRICOPEPTIDE REPEATS
- SELECTIVE-INHIBITION