8af2

Structural highlights

Disease

DHB4_HUMAN Defects in HSD17B4 are a cause of D-bifunctional protein deficiency (DBPD) [MIM:261515. DBPD is a disorder of peroxisomal fatty acid beta-oxidation.^{[1] [2] [3]} Defects in HSD17B4 are the cause of Perrault syndrome (PRLTS1) [MIM:233400. A sex-influenced disorder characterized by sensorineural deafness in both males and females and ovarian dysgenesis in females. Some patients also have neurologic manifestations, including mild mental retardation and cerebellar and peripheral nervous system involvement.^[4]

Function

DHB4_HUMAN Bifunctional enzyme acting on the peroxisomal beta-oxidation pathway for fatty acids. Catalyzes the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids.^{[5] [6]}

References

1. ↑ van Grunsven EG, van Berkel E, Ijlst L, Vreken P, de Klerk JB, Adamski J, Lemonde H, Clayton PT, Cuebas DA, Wanders RJ. Peroxisomal D-hydroxyacyl-CoA dehydrogenase deficiency: resolution of the enzyme defect and its molecular basis in bifunctional protein deficiency. Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2128-33. PMID:9482850
2. ↑ van Grunsven EG, Mooijer PA, Aubourg P, Wanders RJ. Enoyl-CoA hydratase deficiency: identification of a new type of D-bifunctional protein deficiency. Hum Mol Genet. 1999 Aug;8(8):1509-16. PMID:10400999
3. ↑ Nakano K, Zhang Z, Shimozawa N, Kondo N, Ishii N, Funatsuka M, Shirakawa S, Itoh M, Takashima S, Une M, Kana-aki RR, Mukai K, Osawa M, Suzuki Y. D-bifunctional protein deficiency with fetal ascites, polyhydramnios, and contractures of hands and toes. J Pediatr. 2001 Dec;139(6):865-7. PMID:11743515 doi:10.1067/mpd.2001.119170
4. ↑ Pierce SB, Walsh T, Chisholm KM, Lee MK, Thornton AM, Fiumara A, Opitz JM, Levy-Lahad E, Klevit RE, King MC. Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome. Am J Hum Genet. 2010 Aug 13;87(2):282-8. doi: 10.1016/j.ajhg.2010.07.007. Epub, 2010 Jul 30. PMID:20673864 doi:10.1016/j.ajhg.2010.07.007
5. ↑ Jiang LL, Miyazawa S, Souri M, Hashimoto T. Structure of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein. J Biochem. 1997 Feb;121(2):364-9. PMID:9089413
6. ↑ Jiang LL, Kobayashi A, Matsuura H, Fukushima H, Hashimoto T. Purification and properties of human D-3-hydroxyacyl-CoA dehydratase: medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase. J Biochem. 1996 Sep;120(3):624-32. PMID:8902629