Crystal Structure of NADPH-Cytochrome P450 Reductase (FAD/NADPH domain)Crystal Structure of NADPH-Cytochrome P450 Reductase (FAD/NADPH domain)

Structural highlights

3qfs is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.4Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

NCPR_HUMAN Defects in POR are the cause of Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (ABS1) [MIM:201750. A disease characterized by the association of Antley-Bixler syndrome with steroidogenesis defects and abnormal genitalia. Antley-Bixler syndrome is characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures.[1] [2] [3] Defects in POR are the cause of disordered steroidogenesis due to cytochrome P450 oxidoreductase deficiency (DISPORD) [MIM:613571. A disorder resulting in a rare variant of congenital adrenal hyperplasia, with apparent combined P450C17 and P450C21 deficiency and accumulation of steroid metabolites. Affected girls are born with ambiguous genitalia, but their circulating androgens are low and virilization does not progress. Conversely, affected boys are sometimes born undermasculinized. Boys and girls can present with bone malformations, in some cases resembling the pattern seen in patients with Antley-Bixler syndrome.[4] [5]

Function

NCPR_HUMAN This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.

See Also

References

  1. Adachi M, Tachibana K, Asakura Y, Yamamoto T, Hanaki K, Oka A. Compound heterozygous mutations of cytochrome P450 oxidoreductase gene (POR) in two patients with Antley-Bixler syndrome. Am J Med Genet A. 2004 Aug 1;128A(4):333-9. PMID:15264278 doi:10.1002/ajmg.a.30169
  2. Fukami M, Horikawa R, Nagai T, Tanaka T, Naiki Y, Sato N, Okuyama T, Nakai H, Soneda S, Tachibana K, Matsuo N, Sato S, Homma K, Nishimura G, Hasegawa T, Ogata T. Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis: molecular and clinical studies in 10 patients. J Clin Endocrinol Metab. 2005 Jan;90(1):414-26. Epub 2004 Oct 13. PMID:15483095 doi:jc.2004-0810
  3. Fluck CE, Tajima T, Pandey AV, Arlt W, Okuhara K, Verge CF, Jabs EW, Mendonca BB, Fujieda K, Miller WL. Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. Nat Genet. 2004 Mar;36(3):228-30. Epub 2004 Feb 1. PMID:14758361 doi:10.1038/ng1300
  4. Fluck CE, Tajima T, Pandey AV, Arlt W, Okuhara K, Verge CF, Jabs EW, Mendonca BB, Fujieda K, Miller WL. Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. Nat Genet. 2004 Mar;36(3):228-30. Epub 2004 Feb 1. PMID:14758361 doi:10.1038/ng1300
  5. Arlt W, Walker EA, Draper N, Ivison HE, Ride JP, Hammer F, Chalder SM, Borucka-Mankiewicz M, Hauffa BP, Malunowicz EM, Stewart PM, Shackleton CH. Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study. Lancet. 2004 Jun 26;363(9427):2128-35. PMID:15220035 doi:10.1016/S0140-6736(04)16503-3

3qfs, resolution 1.40Å

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