| Structural highlights
1apz is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , ,
| | Activity: | N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase, with EC number 3.5.1.26 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[ASPG_HUMAN] Defects in AGA are the cause of aspartylglucosaminuria (AGU) [MIM:208400]. AGU is an inborn lysosomal storage disease. Clinical features of AGU include mild to severe mental retardation manifesting from the age of 2, coarse facial features and mild connective tissue abnormalities. This recessively inherited disease is overrepresented in the Finnish population.[1] [2] [3] [4] [5] [6]
Function
[ASPG_HUMAN] Cleaves the GlcNAc-Asn bond which joins oligosaccharides to the peptide of asparagine-linked glycoproteins.
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
The high resolution crystal structure of human lysosomal aspartylglucosaminidase (AGA) has been determined. This lysosomal enzyme is synthesized as a single polypeptide precursor, which is immediately post-translationally cleaved into alpha- and beta-subunits. Two alpha- and beta-chains are found to pack together forming the final heterotetrameric structure. The catalytically essential residue, the N-terminal threonine of the beta-chain is situated in the deep pocket of the funnel-shaped active site. On the basis of the structure of the enzyme-product complex we present a catalytic mechanism for this lysosomal enzyme with an exceptionally high pH optimum. The three-dimensional structure also allows the prediction of the structural consequences of human mutations resulting in aspartylglucosaminuria (AGU), a lysosomal storage disease.
Three-dimensional structure of human lysosomal aspartylglucosaminidase.,Oinonen C, Tikkanen R, Rouvinen J, Peltonen L Nat Struct Biol. 1995 Dec;2(12):1102-8. PMID:8846222[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ikonen E, Baumann M, Gron K, Syvanen AC, Enomaa N, Halila R, Aula P, Peltonen L. Aspartylglucosaminuria: cDNA encoding human aspartylglucosaminidase and the missense mutation causing the disease. EMBO J. 1991 Jan;10(1):51-8. PMID:1703489
- ↑ Fisher KJ, Aronson NN Jr. Characterization of the mutation responsible for aspartylglucosaminuria in three Finnish patients. Amino acid substitution Cys163----Ser abolishes the activity of lysosomal glycosylasparaginase and its conversion into subunits. J Biol Chem. 1991 Jun 25;266(18):12105-13. PMID:1904874
- ↑ Mononen I, Heisterkamp N, Kaartinen V, Williams JC, Yates JR 3rd, Griffin PR, Hood LE, Groffen J. Aspartylglycosaminuria in the Finnish population: identification of two point mutations in the heavy chain of glycoasparaginase. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2941-5. PMID:2011603
- ↑ Peltola M, Tikkanen R, Peltonen L, Jalanko A. Ser72Pro active-site disease mutation in human lysosomal aspartylglucosaminidase: abnormal intracellular processing and evidence for extracellular activation. Hum Mol Genet. 1996 Jun;5(6):737-43. PMID:8776587
- ↑ Laitinen A, Hietala M, Haworth JC, Schroeder ML, Seargeant LE, Greenberg CR, Aula P. Two novel mutations in a Canadian family with aspartylglucosaminuria and early outcome post bone marrow transplantation. Clin Genet. 1997 Mar;51(3):174-8. PMID:9137882
- ↑ Saarela J, Laine M, Oinonen C, von Schantz C, Jalanko A, Rouvinen J, Peltonen L. Molecular pathogenesis of a disease: structural consequences of aspartylglucosaminuria mutations. Hum Mol Genet. 2001 Apr 15;10(9):983-95. PMID:11309371
- ↑ Oinonen C, Tikkanen R, Rouvinen J, Peltonen L. Three-dimensional structure of human lysosomal aspartylglucosaminidase. Nat Struct Biol. 1995 Dec;2(12):1102-8. PMID:8846222
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