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Structural highlights

Disease

CP1B1_HUMAN Peters anomaly;Congenital glaucoma;Primary adult open-angle glaucoma;Juvenile glaucoma. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. CYP1B1 mutations have been reported to pose a significant risk for early-onset POAG and also modify glaucoma phenotype in patients who do not carry a MYOC mutation (PubMed:15342693).^[1] The gene represented in this entry acts as a disease modifier. Digenic mutations in CYP1B1 and MYOC have been found in a family segregating both primary adult-onset and juvenile forms of open angle glaucoma (PubMed:11774072). All affected family members with mutations in both MYOC and CYP1B1 had juvenile glaucoma, whereas those with only the MYOC mutation had the adult-onset form (PubMed:11774072).^[2]

Function

CP1B1_HUMAN Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compounds to their activated forms, including polycyclic aromatic hydrocarbons. Promotes angiogenesis by removing cellular oxygenation products, thereby decreasing oxidative stress, release of antiangiogenic factor THBS2, then allowing endothelial cells migration, cell adhesion and capillary morphogenesis. These changes are concommitant with the endothelial nitric oxide synthase activity and nitric oxide synthesis. Plays an important role in the regulation of perivascular cell proliferation, migration, and survival through modulation of the intracellular oxidative state and NF-kappa-B expression and/or activity, during angiogenesis. Contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression.^{[3] [4] [5] [6]}

See Also

• Cytochrome P450 3D structures

References

1. ↑ Melki R, Colomb E, Lefort N, Brezin AP, Garchon HJ. CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma. J Med Genet. 2004 Sep;41(9):647-51. PMID:15342693 doi:http://dx.doi.org/10.1136/jmg.2004.020024
2. ↑ Vincent AL, Billingsley G, Buys Y, Levin AV, Priston M, Trope G, Williams-Lyn D, Heon E. Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene. Am J Hum Genet. 2002 Feb;70(2):448-60. Epub 2002 Jan 3. PMID:11774072 doi:http://dx.doi.org/10.1086/338709
3. ↑ Shimada T, Watanabe J, Kawajiri K, Sutter TR, Guengerich FP, Gillam EM, Inoue K. Catalytic properties of polymorphic human cytochrome P450 1B1 variants. Carcinogenesis. 1999 Aug;20(8):1607-13. PMID:10426814
4. ↑ Choudhary D, Jansson I, Stoilov I, Sarfarazi M, Schenkman JB. Metabolism of retinoids and arachidonic acid by human and mouse cytochrome P450 1b1. Drug Metab Dispos. 2004 Aug;32(8):840-7. PMID:15258110
5. ↑ Jang HH, Kim SY, Kang JY, Park SH, Ryu SH, Ahn T, Yun CH. Increase of human CYP1B1 activities by acidic phospholipids and kinetic deuterium isotope effects on CYP1B1 substrate oxidation. J Biochem. 2012 Nov;152(5):433-42. doi: 10.1093/jb/mvs087. Epub 2012 Aug 9. PMID:22888116 doi:http://dx.doi.org/10.1093/jb/mvs087
6. ↑ Nishida CR, Everett S, Ortiz de Montellano PR. Specificity determinants of CYP1B1 estradiol hydroxylation. Mol Pharmacol. 2013 Sep;84(3):451-8. doi: 10.1124/mol.113.087700. Epub 2013 Jul, 2. PMID:23821647 doi:http://dx.doi.org/10.1124/mol.113.087700