4r4y

Structural basis of a point mutation that causes the genetic disease Aspartylglucosaminuria

spinqualitylabelsall models 4r4y, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4r4y is a 2 chain structure with sequence from Chryseobacterium mirecola. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SD4 Activity: N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase, with EC number 3.5.1.26 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ASPG_ELIMR] Cleaves the GlcNAc-Asn bond which joins oligosaccharides to the peptide of asparagine-linked glycoproteins. Requires that the glycosylated asparagine moiety is not substituted on its N-(R1) and C- (R2) terminus. Publication Abstract from PubMed Aspartylglucosaminuria (AGU) is a lysosomal storage disease caused by a metabolic disorder of lysosomes to digest Asn-linked glycoproteins. The specific enzyme linked to AGU is a lysosomal hydrolase called glycosylasparaginase. Crystallographic studies revealed that a surface loop blocks the catalytic center of the mature hydrolase. Autoproteolysis is therefore required to remove this P loop and open up the hydrolase center. Nonetheless, AGU mutations result in misprocessing of their precursors and are deficient in hydrolyzing glycoasparagines. To understand the catalytic and structural consequences of AGU mutations, we have characterized two AGU models, one corresponding to a Finnish allele and the other found in a Canadian family. We also report a 2.1 A resolution structure of the latter AGU model. The current crystallographic study provides a high-resolution structure of an AGU mutant. It reveals substantial conformation changes at the defective autocleavage site of the AGU mutant, which is trapped as an inactive precursor. Structural Basis of a Point Mutation that Causes the Genetic Disease Aspartylglucosaminuria.,Sui L, Lakshminarasimhan D, Pande S, Guo HC Structure. 2014 Dec 2;22(12):1855-61. doi: 10.1016/j.str.2014.09.014. Epub 2014, Nov 13. PMID:25456816 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Asparaginase 3D structures

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