Journal article

Structure of human endo-alpha-1,2-mannosidase (MANEA), an antiviral host-glycosylation target

Lukasz F Sobala, Pearl Z Fernandes, Zalihe Hakki, Andrew J Thompson, Jonathon D Howe, Michelle Hill, Nicole Zitzmann, Scott Davies, Zania Stamataki, Terry D Butters, Dominic S Alonzi, Spencer J Williams, Gideon J Davies

Proceedings of the National Academy of Sciences of the United States of America | National Academy of Sciences | Published : 2020


Mammalian protein N-linked glycosylation is critical for glycoprotein folding, quality control, trafficking, recognition, and function. N-linked glycans are synthesized from Glc3Man9GlcNAc2 precursors that are trimmed and modified in the endoplasmic reticulum (ER) and Golgi apparatus by glycoside hydrolases and glycosyltransferases. Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II. There is considerable interest in the use of small molecules that disrupt N-linked glycosylat..

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University of Melbourne Researchers


Awarded by European Research Council

Awarded by Australian Research Council

Funding Acknowledgements

We thank Jon Agirre for assistance with generating a dictionary file for TEW, Eleanor Dodson for assistance with processing the highly anisotropic datasets, Alexandra Males for collecting ITC data with Glc-DMJ, and Mahima Sharma for assisting with supplemental figure production. We also thank Diamond Light Source UK for access to beamlines I03, I04, and I24 (Proposals mx1221, mx12587, and mx18598). Support for this work was provided by the European Research Council (ERC-2012-AdG-32294, "Glycopoise"), the Australian Research Council (DP120101396, FT130100103, and DP180101957), and the Royal Society (a Ken Murray Research Professorship, to G.J.D.).