Connecting chemistry to biology to understand why O‐GlcNAc transferase is essential

다국어 초록 (Multilingual Abstract)

O‐GlcNAc transferase (OGT) is an essential mammalian enzyme that catalyzes two fundamentally different, physiologically relevant chemical reactions using the same active site. One reaction is the transfer of N‐acetyl glucosamine to Ser/Thr side chains of nuclear and cytoplasmic proteins. OGT uniquely O‐GlcNAcylates myriad intracellular proteins involved in cell growth and division in a nutrient‐ and stress‐responsive manner, attracting comparisons between it and mTOR. The second reaction is polypeptide backbone cleavage. OGT is required for the proteolytic maturation of another essential mammalian protein, Host Cell Factor 1, a transcriptional co‐regulator found in a number of chromatin‐associated complexes. Understanding OGT's complex biology requires first understanding its chemistry well enough to separate its functions and then developing genetic approaches to replace wildtype OGT with well‐characterized variants. We will talk about our published structural and mechanistic work to understand how OGT catalyzes glycosylation and peptide backbone cleavage, and will also describe recent results that reveal how it chooses many of its substrates. We will then describe how we have combined this knowledge with a genetic system to replace OGT in cells in order to begin to address a key question: why is OGT essential in all dividing mammalian cells?
Support or Funding Information
Funding for this work was provided by a National Institutes of Health grant (R01 GM094263)
This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.