| Structural highlights
1aos 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.
| | Activity: | Argininosuccinate lyase, with EC number 4.3.2.1 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[ARLY_HUMAN] Defects in ASL are the cause of arginosuccinic aciduria (ARGINSA) [MIM:207900]. An autosomal recessive disorder of the urea cycle. The disease is characterized by mental and physical retardation, liver enlargement, skin lesions, dry and brittle hair showing trichorrhexis nodosa microscopically and fluorescing red, convulsions, and episodic unconsciousness.[1] [2] [3] [4]
Function
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
Intragenic complementation has been observed at the argininosuccinate lyase (ASL) locus. Intragenic complementation is a phenomenon that occurs when a multimeric protein is formed from subunits produced by different mutant alleles of a gene. The resulting hybrid protein exhibits enzymatic activity that is greater than that found in the oligomeric proteins produced by each mutant allele alone. The mutations involved in the most successful complementation event observed in ASL deficiency were found to be an aspartate to glycine mutation at codon 87 of one allele (D87G) coupled with a glutamine to arginine mutation at codon 286 of the other (Q286R). To understand the structural basis of the Q286R:D87G intragenic complementation event at the ASL locus, we have determined the x-ray crystal structure of recombinant human ASL at 4. 0 A resolution. The structure has been refined to an R factor of 18. 8%. Two monomers related by a noncrystallographic 2-fold axis comprise the asymmetric unit, and a crystallographic 2-fold axis of space group P3121 completes the tetramer. Each of the four active sites is composed of residues from three monomers. Structural mapping of the Q286R and D87G mutations indicate that both are near the active site and each is contributed by a different monomer. Thus when mutant monomers combine randomly such that one active site contains both mutations, it is required by molecular symmetry that another active site exists with no mutations. These "native" active sites give rise to the observed partial recovery of enzymatic activity.
Human argininosuccinate lyase: a structural basis for intragenic complementation.,Turner MA, Simpson A, McInnes RR, Howell PL Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9063-8. PMID:9256435[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Barbosa P, Cialkowski M, O'Brien WE. Analysis of naturally occurring and site-directed mutations in the argininosuccinate lyase gene. J Biol Chem. 1991 Mar 15;266(8):5286-90. PMID:1705937
- ↑ Walker DC, McCloskey DA, Simard LR, McInnes RR. Molecular analysis of human argininosuccinate lyase: mutant characterization and alternative splicing of the coding region. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9625-9. PMID:2263616
- ↑ Kleijer WJ, Garritsen VH, Linnebank M, Mooyer P, Huijmans JG, Mustonen A, Simola KO, Arslan-Kirchner M, Battini R, Briones P, Cardo E, Mandel H, Tschiedel E, Wanders RJ, Koch HG. Clinical, enzymatic, and molecular genetic characterization of a biochemical variant type of argininosuccinic aciduria: prenatal and postnatal diagnosis in five unrelated families. J Inherit Metab Dis. 2002 Sep;25(5):399-410. PMID:12408190
- ↑ Trevisson E, Salviati L, Baldoin MC, Toldo I, Casarin A, Sacconi S, Cesaro L, Basso G, Burlina AB. Argininosuccinate lyase deficiency: mutational spectrum in Italian patients and identification of a novel ASL pseudogene. Hum Mutat. 2007 Jul;28(7):694-702. PMID:17326097 doi:10.1002/humu.20498
- ↑ Turner MA, Simpson A, McInnes RR, Howell PL. Human argininosuccinate lyase: a structural basis for intragenic complementation. Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9063-8. PMID:9256435
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