Structural highlights
Publication Abstract from PubMed
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 beta-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.
Bacterial beta-Glucosidase Reveals the Structural and Functional Basis of Genetic Defects in Human Glucocerebrosidase 2 (GBA2).,Charoenwattanasatien R, Pengthaisong S, Breen I, Mutoh R, Sansenya S, Hua Y, Tankrathok A, Wu L, Songsiriritthigul C, Tanaka H, Williams SJ, Davies GJ, Kurisu G, Cairns JR ACS Chem Biol. 2016 May 6. PMID:27115290[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Charoenwattanasatien R, Pengthaisong S, Breen I, Mutoh R, Sansenya S, Hua Y, Tankrathok A, Wu L, Songsiriritthigul C, Tanaka H, Williams SJ, Davies GJ, Kurisu G, Cairns JR. Bacterial beta-Glucosidase Reveals the Structural and Functional Basis of Genetic Defects in Human Glucocerebrosidase 2 (GBA2). ACS Chem Biol. 2016 May 6. PMID:27115290 doi:http://dx.doi.org/10.1021/acschembio.6b00192
