4mhx | pdb_00004mhx

Crystal Structure of Sulfamidase

spinqualitylabelsall models 4mhx, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4mhx 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 2Å Ligands: CA, FGP, MG, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease SPHM_HUMAN Sanfilippo syndrome type A. The disease is caused by mutations affecting the gene represented in this entry. Function SPHM_HUMAN Publication Abstract from PubMed Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 A resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder. Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA.,Sidhu NS, Schreiber K, Propper K, Becker S, Uson I, Sheldrick GM, Gartner J, Kratzner R, Steinfeld R Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1321-35. doi:, 10.1107/S1399004714002739. Epub 2014 Apr 30. PMID:24816101 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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