2vt0 | pdb_00002vt0

X-ray structure of a conjugate with conduritol-beta-epoxide of acid-beta-glucosidase overexpressed in cultured plant cells

spinqualitylabelsall models 2vt0, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2vt0 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.15Å Ligands: CBU, FUC, MAN, NAG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GLCM_HUMAN Defects in GBA are the cause of Gaucher disease (GD) [MIM:230800; also known as glucocerebrosidase deficiency. GD is the most prevalent lysosomal storage disease, characterized by accumulation of glucosylceramide in the reticulo-endothelial system. Different clinical forms are recognized depending on the presence (neuronopathic forms) or absence of central nervous system involvement, severity and age of onset. [:] Defects in GBA are the cause of Gaucher disease type 1 (GD1) [MIM:230800; also known as adult non-neuronopathic Gaucher disease. GD1 is characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved.[:] Defects in GBA are the cause of Gaucher disease type 2 (GD2) [MIM:230900; also known as acute neuronopathic Gaucher disease. GD2 is the most severe form and is universally progressive and fatal. It manifests soon after birth, with death generally occurring before patients reach two years of age. Defects in GBA are the cause of Gaucher disease type 3 (GD3) [MIM:231000; also known as subacute neuronopathic Gaucher disease. GD3 has central nervous manifestations. Defects in GBA are the cause of Gaucher disease type 3C (GD3C) [MIM:231005; also known as pseudo-Gaucher disease or Gaucher-like disease. Defects in GBA are the cause of Gaucher disease perinatal lethal (GDPL) [MIM:608013. It is a distinct form of Gaucher disease type 2, characterized by fetal onset. Hydrops fetalis, in utero fetal death and neonatal distress are prominent features. When hydrops is absent, neurologic involvement begins in the first week and leads to death within 3 months. Hepatosplenomegaly is a major sign, and is associated with ichthyosis, arthrogryposis, and facial dysmorphism. Note=Perinatal lethal Gaucher disease is associated with non-immune hydrops fetalis, a generalized edema of the fetus with fluid accumulation in the body cavities due to non-immune causes. Non-immune hydrops fetalis is not a diagnosis in itself but a symptom, a feature of many genetic disorders, and the end-stage of a wide variety of disorders. Defects in GBA contribute to susceptibility to Parkinson disease (PARK) [MIM:168600. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features. Function GLCM_HUMAN Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed In mammalian cells, glucosylceramide (GlcCer), the simplest glycosphingolipid, is hydrolyzed by the lysosomal enzyme acid beta-glucosidase (GlcCerase). In the human metabolic disorder Gaucher disease, GlcCerase activity is significantly decreased owing to one of approximately 200 mutations in the GlcCerase gene. The most common therapy for Gaucher disease is enzyme replacement therapy (ERT), in which patients are given intravenous injections of recombinant human GlcCerase; the Genzyme product Cerezyme has been used clinically for more than 15 years and is administered to approximately 4000 patients worldwide. Here we review the crystal structure of Cerezyme and other recombinant forms of GlcCerase, as well as of their complexes with covalent and non-covalent inhibitors. We also discuss the stability of Cerezyme, which can be altered by modification of its N-glycan chains with possible implications for improved ERT in Gaucher disease. Acid beta-glucosidase: insights from structural analysis and relevance to Gaucher disease therapy.,Kacher Y, Brumshtein B, Boldin-Adamsky S, Toker L, Shainskaya A, Silman I, Sussman JL, Futerman AH Biol Chem. 2008 Nov;389(11):1361-9. PMID:18783340 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acid-beta-glucosidase 3D structures

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