Structural analyses of enzymes involved in the O-GlcNAc modification.
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.
Martinez-Fleites
Carlos
C
York Structural Biology Laboratory, Department of Chemistry, The University of York, Heslington, York, YO10 5YW, UK.
He
Yuan
Y
Davies
Gideon J
GJ
D000118:Acetylglucosaminidase / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013844:Thiazoles / Q000737:chemistry
D013844:Thiazoles; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D000118:Acetylglucosaminidase