Phosphoglycosyl transferases (PGTs) play a pivotal role at the inception of complex glycoconjugate biosynthesis pathways across all domains of life. PGTs promote the first membrane-committed step in the en bloc biosynthetic strategy by catalyzing the transfer of a phospho-sugar from a nucleoside diphospho-sugar to a membrane-resident polyprenol phosphate. Studies on the PGTs have been hampered because they are integral membrane proteins, and often prove to be recalcitrant to expression, purification and analysis. However, in recent years exciting new information has been derived on the structures and the mechanisms of PGTs, revealing the existence of two unique superfamilies of PGT enzymes that enact catalysis at the membrane interface. Genome neighborhood analysis shows that these superfamilies, the polytopic PGT (polyPGT) and monotopic PGT (monoPGT), may initiate different pathways within the same organism. Moreover, the same fundamental two-substrate reaction is enacted through two different chemical mechanisms with distinct modes of catalysis. This review highlights the structural and mechanistic divergence between the PGT enzyme superfamilies and how this is reflected in differences in regulation in their varied glycoconjugate biosynthesis pathways.
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Cover Image
Cover Image
Depicted as playing cards belonging to the same suit, the paralogous MLL3 and MLL4 lysine methyltransferase (KMT) complexes share a common set of core and auxiliary subunits as well as similar histone methylase functions. On each card, largely divergent processes are described on opposing sides – highlighting the potential capacity of these KMT complexes to participate in both tumor-supportive and tumor-suppressive mechanisms. To understand how MLL3 and MLL4 can regulate such diverse and sometimes contrasting processes, read more in this review article by Wang and colleagues (pp. 1041–1054). Cover artwork created by Marvin Aberin with Biorender.com.
The surprising structural and mechanistic dichotomy of membrane-associated phosphoglycosyl transferases
Katherine H. O'Toole, Hannah M. Bernstein, Karen N. Allen, Barbara Imperiali; The surprising structural and mechanistic dichotomy of membrane-associated phosphoglycosyl transferases. Biochem Soc Trans 30 June 2021; 49 (3): 1189–1203. doi: https://doi.org/10.1042/BST20200762
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