2V3F

acid-beta-glucosidase produced in carrot

2V3F の概要

• エントリーDOI: 10.2210/pdb2v3f/pdb
• 関連するPDBエントリー: 1OGS 1Y7V 2F61 2J25 2V3D 2V3E
• 分子名称: GLUCOSYLCERAMIDASE, alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-3)]2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-L-fucopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: alternative initiation, sphingolipid metabolism, gaucher disease, disease mutation, lipid metabolism, polymorphism, glycoprotein, pharmaceutical, n-butyl-deoxynojirimycin, alternative splicing, acid-beta-glucosidase, membrane, lysosome, hydrolase, glycosidase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 116053.03

構造登録者

Shaaltiel, Y.,Bartfeld, D.,Hashmueli, S.,Baum, G.,Brill-Almon, E.,Galili, G.,Dym, O.,Boldin-Adamsky, S.A.,Silman, I.,Sussman, J.L.,Futerman, A.H.,Aviezer, D.,Israel Structural Proteomics Center (ISPC) (登録日: 2007-06-17, 公開日: 2008-04-08, 最終更新日: 2024-10-23)

主引用文献

Shaaltiel, Y.,Bartfeld, D.,Hashmueli, S.,Baum, G.,Brill-Almon, E.,Galili, G.,Dym, O.,Boldin-Adamsky, S.A.,Silman, I.,Sussman, J.L.,Futerman, A.H.,Aviezer, D.
Production of Glucocerebrosidase with Terminal Mannose Glycans for Enzyme Replacement Therapy of Gaucher'S Disease Using a Plant Cell System.
Plant Biotechnol.J., 5:579-, 2007

PubMed Abstract: Gaucher's disease, a lysosomal storage disorder caused by mutations in the gene encoding glucocerebrosidase (GCD), is currently treated by enzyme replacement therapy using recombinant GCD (Cerezyme) expressed in Chinese hamster ovary (CHO) cells. As complex glycans in mammalian cells do not terminate in mannose residues, which are essential for the biological uptake of GCD via macrophage mannose receptors in human patients with Gaucher's disease, an in vitro glycan modification is required in order to expose the mannose residues on the glycans of Cerezyme. In this report, the production of a recombinant human GCD in a carrot cell suspension culture is described. The recombinant plant-derived GCD (prGCD) is targeted to the storage vacuoles, using a plant-specific C-terminal sorting signal. Notably, the recombinant human GCD expressed in the carrot cells naturally contains terminal mannose residues on its complex glycans, apparently as a result of the activity of a special vacuolar enzyme that modifies complex glycans. Hence, the plant-produced recombinant human GCD does not require exposure of mannose residues in vitro, which is a requirement for the production of Cerezyme. prGCD also displays a level of biological activity similar to that of Cerezyme produced in CHO cells, as well as a highly homologous high-resolution three-dimensional structure, determined by X-ray crystallography. A single-dose toxicity study with prGCD in mice demonstrated the absence of treatment-related adverse reactions or clinical findings, indicating the potential safety of prGCD. prGCD is currently undergoing clinical studies, and may offer a new and alternative therapeutic option for Gaucher's disease.

PubMed: 17524049
DOI: 10.1111/J.1467-7652.2007.00263.X

実験手法

X-RAY DIFFRACTION (1.95 Å)