Biomaterial Database

Discovery of O-GlcNAc transferase inhibitors. 2005

Benjamin J Gross, and Brian C Kraybill, and Suzanne Walker

Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.

O-GlcNAcylation of serine and threonine residues is a dynamic and essential post-translational modification involved in signaling pathways in eukaryotes. Studies of O-GlcNAcylation would be aided by small-molecule inhibitors of O-GlcNAc transferase (OGT), the sole enzyme know to mediate this modification, but discovery of such molecules has been hampered by poor expression of cloned OGT and lack of suitable high-throughput screens. This Communication describes the development an expression system to access large amounts of the catalytic domain of OGT and the implementation of a fluorescence-based substrate analogue displacement assay that has led to the discovery of a set of OGT inhibitors. This work lays the foundation for both structural and functional analysis of the catalytic domain of OGT.

UI	MeSH Term	Description	Entries
D002384	Catalysis	The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.	Catalyses
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D004926	Escherichia coli	A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.	Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular
D017351	N-Acetylglucosaminyltransferases	Enzymes that catalyze the transfer of N-acetylglucosamine from a nucleoside diphosphate N-acetylglucosamine to an acceptor molecule which is frequently another carbohydrate. EC 2.4.1.-.	N-Acetylglucosamine Transferases,N Acetylglucosamine Transferases,N Acetylglucosaminyltransferases,Transferases, N-Acetylglucosamine