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Three-dimensional structure of human lysosomal aspartylglucosaminidase

Nature Structural Biology volume 2, pages 1102–1108 (1995)Cite this article

Abstract

The high resolution crystal structure of human lysosomal aspartylglucosaminidase (AGA) has been determined. This lysosomal enzyme is synthesized as a single polypeptide precursor, which is immediately post-translationally cleaved into α- and β-subunits. Two α- and β-chains are found to pack together forming the final heterotetrameric structure. The catalytically essential residue, the N-terminal threonine of the β-chain is situated in the deep pocket of the funnel-shaped active site. On the basis of the structure of the enzyme–product complex we present a catalytic mechanism for this lysosomal enzyme with an exceptionally high pH optimum. The three-dimensional structure also allows the prediction of the structural consequences of human mutations resulting in aspartylglucosaminuria (AGU), a lysosomal storage disease.

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Authors and Affiliations

  1. Department of Chemistry, University of Joensuu, P.O. Box 111, FIN-80101, Joensuu, Finland

    Carita Oinonen & Juha Rouvinen

  2. Department of Human Molecular Genetics, National Public Health Institute, Mannerheimintie 166, FIN-00300, Helsinki, Finland

    Ritva Tikkanen & Leena Peltonen

Authors
  1. Carita Oinonen
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  2. Ritva Tikkanen
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  3. Juha Rouvinen
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  4. Leena Peltonen
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Oinonen, C., Tikkanen, R., Rouvinen, J. et al. Three-dimensional structure of human lysosomal aspartylglucosaminidase. Nat Struct Mol Biol 2, 1102–1108 (1995). https://doi.org/10.1038/nsb1295-1102

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