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Bacterial β-Glucosidase Reveals the Structural and Functional Basis of Genetic Defects in Human Glucocerebrosidase 2 (GBA2)

DOI: 10.1021/acschembio.6b00192 DOI Help

Authors: Ratana Charoenwattanasatien (Osaka University) , Salila Pengthaisong (Suranaree Univerity of Technology) , Imogen Breen (University of York) , Risa Mutoh (Osaka University) , Sompong Sansenya (Rajamangala University of Technology) , Yanling Hua (Suranaree University of Technology) , Anupong Tankrathok (Kalasin University) , Liang Wu (The University of York) , Chomphunuch Songsiriritthigul (Suranaree University of Technology) , Hideaki Tanaka (Osaka University) , Spencer J. Williams (University of Melbourne) , Gideon Davies (University of York) , Genji Kurisu (Osaka University) , James R. Ketudat Cairns (Suranaree Univerity of Technology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acs Chemical Biology

State: Published (Approved)
Published: May 2016

Abstract: Human glucosylcerebrosidase 2 (GBA2) of the CAZy family GH116 is responsible for the breakdown of glycosphingolipids on the cytoplasmic face of the endoplasmic reticulum and Golgi apparatus. Genetic defects in GBA2 result in spastic paraplegia and cerebellar ataxia, while cross-talk between GBA2 and GBA1 glucosylceramidases may affect Gaucher disease. Here, we report the first three-dimensional structure for any GH116 enzyme, Thermoanaerobacterium xylanolyticum TxGH116 β-glucosidase, alone and in complex with diverse ligands. These structures allow identification of the glucoside binding and active site residues, which are shown to be conserved with GBA2. Mutagenic analysis of TxGH116 and structural modeling of GBA2 provide a detailed structural and functional rationale for pathogenic missense mutations of GBA2.

Subject Areas: Biology and Bio-materials


Instruments: I24-Microfocus Macromolecular Crystallography

Other Facilities: Spring8

Added On: 17/05/2016 16:52

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