Mechanism, Structure, and Inhibition of O-GlcNAc Processing Enzymes

Tracey M. Gloster, David J. Vocadlo

Research output: Contribution to journalReview articlepeer-review

42 Citations (Scopus)

Abstract

The post-translational modification of nucleocytoplasmic proteins with O-linked 2-acetamido-2-deoxy-D-glucopyranose (O-GlcNAc) is a topic of considerable interest and attracts a great deal of research effort. O-GlcNAcylation is a dynamic process which can occur multiple times over the lifetime of a protein, sometimes in a reciprocal relationship with phosphorylation. Several hundred proteins, which are involved in a diverse range of cellular processes, have been identified as being modified with the monosaccharide. The control of the O-GlcNAc modification state on different protein targets appears to be important in the aetiology of a number of diseases, including type II diabetes, neurodegenerative diseases and cancer. Two enzymes are responsible for the addition and removal of the O-GlcNAc modification: uridine diphospho-N-acetylglucosamine: polypeptide beta-N-acetylglucosaminyltransferase (OGT) and O-GlcNAcase (OGA), respectively. Over the past decade the volume of information known about these two enzymes has increased significantly. In particular, mechanistic studies of OGA, in conjunction with structural studies of bacterial homologues of OGA have stimulated the design of inhibitors and offered a rationale for the binding of certain potent and selective inhibitors. Mechanistic information about OGT lags a little way behind OGA, but the recent deduction of the structure of an OGT bacterial homologue should now drive these studies forward.

Original languageEnglish
Pages (from-to)74-91
Number of pages18
JournalCurrent Signal Transduction Therapy
Volume5
Issue number1
Publication statusPublished - Jan 2010

Keywords

  • Post-translational modification
  • O-GlcNAc
  • O-GlcNAcase
  • O-GlcNAc transferase
  • enzyme mechanism
  • inhibition
  • three-dimensional structure
  • BETA-N-ACETYLGLUCOSAMINIDASE
  • SUBSTRATE-ASSISTED CATALYSIS
  • TRANSITION-STATE ANALOGS
  • APOPTOTIC CELL-DEATH
  • TAY-SACHS-DISEASE
  • INSULIN-RESISTANCE
  • LINKED GLCNAC
  • D-GLUCOSAMINIDASE
  • HEXOSAMINIDASE-C
  • TRANSFERASE OGT

Fingerprint

Dive into the research topics of 'Mechanism, Structure, and Inhibition of O-GlcNAc Processing Enzymes'. Together they form a unique fingerprint.

Cite this