1hzd

Structural highlights

Disease

AUHM_HUMAN Defects in AUH are the cause of 3-methylglutaconic aciduria type 1 (MGA1) [MIM:250950. MGA1 is an inborn error of leucine metabolism. It leads to an autosomal recessive syndrome with variable clinical phenotype, ranging from delayed speech development to severe psychomotor retardation, coma, failure to thrive, metabolic acidosis and dystonia. MGA1 can be distinguished from other forms of MGA by the pattern of metabolite excretion: 3-methylglutaconic acid levels are higher than those detected in other forms, whereas methylglutaric acid levels are usually only slightly elevated, and there is a high level of 3-hydroxyisovaleric acid excretion (not present in other MGA forms).^{[1] [2]}

Function

AUHM_HUMAN Catalyzes the conversion of 3-methylglutaconyl-CoA to 3-hydroxy-3-methylglutaryl-CoA. Has very low enoyl-CoA hydratase activity. Was originally identified as RNA-binding protein that binds in vitro to clustered 5'-AUUUA-3' motifs.^{[3] [4] [5] [6]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ IJlst L, Loupatty FJ, Ruiter JP, Duran M, Lehnert W, Wanders RJ. 3-Methylglutaconic aciduria type I is caused by mutations in AUH. Am J Hum Genet. 2002 Dec;71(6):1463-6. Epub 2002 Nov 14. PMID:12434311 doi:S0002-9297(07)60868-4
2. ↑ Ly TB, Peters V, Gibson KM, Liesert M, Buckel W, Wilcken B, Carpenter K, Ensenauer R, Hoffmann GF, Mack M, Zschocke J. Mutations in the AUH gene cause 3-methylglutaconic aciduria type I. Hum Mutat. 2003 Apr;21(4):401-7. PMID:12655555 doi:10.1002/humu.10202
3. ↑ Nakagawa J, Waldner H, Meyer-Monard S, Hofsteenge J, Jeno P, Moroni C. AUH, a gene encoding an AU-specific RNA binding protein with intrinsic enoyl-CoA hydratase activity. Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2051-5. PMID:7892223
4. ↑ IJlst L, Loupatty FJ, Ruiter JP, Duran M, Lehnert W, Wanders RJ. 3-Methylglutaconic aciduria type I is caused by mutations in AUH. Am J Hum Genet. 2002 Dec;71(6):1463-6. Epub 2002 Nov 14. PMID:12434311 doi:S0002-9297(07)60868-4
5. ↑ Kurimoto K, Fukai S, Nureki O, Muto Y, Yokoyama S. Crystal structure of human AUH protein, a single-stranded RNA binding homolog of enoyl-CoA hydratase. Structure. 2001 Dec;9(12):1253-63. PMID:11738050
6. ↑ Ly TB, Peters V, Gibson KM, Liesert M, Buckel W, Wilcken B, Carpenter K, Ensenauer R, Hoffmann GF, Mack M, Zschocke J. Mutations in the AUH gene cause 3-methylglutaconic aciduria type I. Hum Mutat. 2003 Apr;21(4):401-7. PMID:12655555 doi:10.1002/humu.10202
7. ↑ Kurimoto K, Fukai S, Nureki O, Muto Y, Yokoyama S. Crystal structure of human AUH protein, a single-stranded RNA binding homolog of enoyl-CoA hydratase. Structure. 2001 Dec;9(12):1253-63. PMID:11738050