4kgl | pdb_00004kgl

Crystal structure of human alpha-L-iduronidase complex with [2R,3R,4R,5S]-2-carboxy-3,4,5-trihydroxy-piperidine

spinqualitylabelsall models 4kgl, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4kgl 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 2.701Å Ligands: BMA, GOL, IDJ, MAN, NAG, TLA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease IDUA_HUMAN Hurler-Scheie syndrome;Hurler syndrome;Scheie syndrome. Defects in IDUA are the cause of mucopolysaccharidosis type 1H (MPS1H) [MIM:607014; also known as Hurler syndrome. MPS1H is a severe form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1H usually present, within the first year of life, a combination of hepatosplenomegaly, skeletal deformities, corneal clouding and severe mental retardation. Obstructive airways disease, respiratory infection and cardiac complications usually result in death before 10 years of age. Defects in IDUA are the cause of mucopolysaccharidosis type 1H/S (MPS1H/S) [MIM:607015; also known as Hurler-Scheie syndrome. MPS1H/S is a form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. MPS1H/S represents an intermediate phenotype of the MPS1 clinical spectrum. It is characterized by relatively little neurological involvement, but most of the somatic symptoms described for severe MPS1 develop in the early to mid-teens, causing considerable loss of mobility. Defects in IDUA are the cause of mucopolysaccharidosis type 1S (MPS1S) [MIM:607016; also known as Scheie syndrome. MPS1S is a mild form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1S may have little or no neurological involvement, normal stature and life span, but present development of joints stiffness, mild hepatosplenomegaly, aortic valve disease and corneal clouding. Function IDUA_HUMAN Publication Abstract from PubMed Mucopolysaccharidosis type I (MPS I), caused by mutations in the gene encoding alpha-L-iduronidase (IDUA), is one of approximately 70 genetic disorders collectively known as the lysosomal storage diseases. To gain insight into the basis for MPS I, we crystallized human IDUA produced in an Arabidopsis thaliana cgl mutant. IDUA consists of a TIM barrel domain containing the catalytic site, a beta-sandwich domain and a fibronectin-like domain. Structures of IDUA bound to iduronate analogs illustrate the Michaelis complex and reveal a 2,5B conformation in the glycosyl-enzyme intermediate, which suggest a retaining double displacement reaction involving the nucleophilic Glu299 and the general acid/base Glu182. Unexpectedly, the N-glycan attached to Asn372 interacts with iduronate analogs in the active site and is required for enzymatic activity. Finally, these IDUA structures and biochemical analysis of the disease-relevant P533R mutation have enabled us to correlate the effects of mutations in IDUA to clinical phenotypes. Insights into mucopolysaccharidosis I from the structure and action of alpha-L-iduronidase.,Bie H, Yin J, He X, Kermode AR, Goddard-Borger ED, Withers SG, James MN Nat Chem Biol. 2013 Sep 11. doi: 10.1038/nchembio.1357. PMID:24036510 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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