| Structural highlights
1wvb is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | Related: | 1wva |
| Activity: | Arginase, with EC number 3.5.3.1 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[ARGI1_HUMAN] Defects in ARG1 are the cause of argininemia (ARGIN) [MIM:207800]; also known as hyperargininemia. Argininemia is a rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia, progressive spastic quadriplegia.[1] [2]
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
The structure of the trimeric, manganese metalloenzyme, rat liver arginase, has been previously determined at 2.1-A resolution (Kanyo, Z. F., Scolnick, L. R., Ash, D. E., and Christianson, D. W., (1996) Nature 383, 554-557). A key feature of this structure is a novel S-shaped oligomerization motif at the carboxyl terminus of the protein that mediates approximately 54% of the intermonomer contacts. Arg-308, located within this oligomerization motif, nucleates a series of intramonomer and intermonomer salt links. In contrast to the trimeric wild-type enzyme, the R308A, R308E, and R308K variants of arginase exist as monomeric species, as determined by gel filtration and analytical ultracentrifugation, indicating that mutation of Arg-308 shifts the equilibrium for trimer dissociation by at least a factor of 10(5). These monomeric arginase variants are catalytically active, with k(cat)/K(m) values that are 13-17% of the value for wild-type enzyme. The arginase variants are characterized by decreased temperature stability relative to the wild-type enzyme. Differential scanning calorimetry shows that the midpoint temperature for unfolding of the Arg-308 variants is in the range of 63.6-65.5 degrees C, while the corresponding value for the wild-type enzyme is 70 degrees C. The three-dimensional structure of the R308K variant has been determined at 3-A resolution. At the high protein concentrations utilized in the crystallizations, this variant exists as a trimer, but weakened salt link interactions are observed for Lys-308.
Subunit-subunit interactions in trimeric arginase. Generation of active monomers by mutation of a single amino acid.,Lavulo LT, Sossong TM Jr, Brigham-Burke MR, Doyle ML, Cox JD, Christianson DW, Ash DE J Biol Chem. 2001 Apr 27;276(17):14242-8. Epub 2001 Jan 24. PMID:11278703[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Uchino T, Haraguchi Y, Aparicio JM, Mizutani N, Higashikawa M, Naitoh H, Mori M, Matsuda I. Three novel mutations in the liver-type arginase gene in three unrelated Japanese patients with argininemia. Am J Hum Genet. 1992 Dec;51(6):1406-12. PMID:1463019
- ↑ Uchino T, Snyderman SE, Lambert M, Qureshi IA, Shapira SK, Sansaricq C, Smit LM, Jakobs C, Matsuda I. Molecular basis of phenotypic variation in patients with argininemia. Hum Genet. 1995 Sep;96(3):255-60. PMID:7649538
- ↑ Lavulo LT, Sossong TM Jr, Brigham-Burke MR, Doyle ML, Cox JD, Christianson DW, Ash DE. Subunit-subunit interactions in trimeric arginase. Generation of active monomers by mutation of a single amino acid. J Biol Chem. 2001 Apr 27;276(17):14242-8. Epub 2001 Jan 24. PMID:11278703 doi:10.1074/jbc.M010575200
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