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Structural highlights

Disease

CP21A_HUMAN Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, simple virilizing form;NON RARE IN EUROPE: Non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency;Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, salt wasting form. The disease is caused by variants affecting the gene represented in this entry.

Function

CP21A_HUMAN A cytochrome P450 monooxygenase that plays a major role in adrenal steroidogenesis. Catalyzes the hydroxylation at C-21 of progesterone and 17alpha-hydroxyprogesterone to respectively form 11-deoxycorticosterone and 11-deoxycortisol, intermediate metabolites in the biosynthetic pathway of mineralocorticoids and glucocorticoids (PubMed:25855791, PubMed:10602386, PubMed:16984992, PubMed:22014889, PubMed:27721825). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:25855791).^{[1] [2] [3] [4] [5]}

See Also

• Cytochrome P450 hydroxylase 3D structures

References

1. ↑ Tajima T, Okada T, Ma XM, Ramsey W, Bornstein S, Aguilera G. Restoration of adrenal steroidogenesis by adenovirus-mediated transfer of human cytochromeP450 21-hydroxylase into the adrenal gland of21-hydroxylase-deficient mice. Gene Ther. 1999 Nov;6(11):1898-903. PMID:10602386 doi:10.1038/sj.gt.3301018
2. ↑ Grischuk Y, Rubtsov P, Riepe FG, Grötzinger J, Beljelarskaia S, Prassolov V, Kalintchenko N, Semitcheva T, Peterkova V, Tiulpakov A, Sippell WG, Krone N. Four novel missense mutations in the CYP21A2 gene detected in Russian patients suffering from the classical form of congenital adrenal hyperplasia: identification, functional characterization, and structural analysis. J Clin Endocrinol Metab. 2006 Dec;91(12):4976-80. PMID:16984992 doi:10.1210/jc.2006-0777
3. ↑ Concolino P, Mello E, Patrosso MC, Penco S, Zuppi C, Capoluongo E. p.H282N and p.Y191H: 2 novel CYP21A2 mutations in Italian congenital adrenal hyperplasia patients. Metabolism. 2012 Apr;61(4):519-24. PMID:22014889 doi:10.1016/j.metabol.2011.08.008
4. ↑ Pallan PS, Wang C, Lei L, Yoshimoto FK, Auchus RJ, Waterman MR, Guengerich FP, Egli M. Human Cytochrome P450 21A2, the Major Steroid 21-Hydroxylase: Structure of the Enzyme-Progesterone Substrate Complex and Rate-Limiting C-H Bond Cleavage. J Biol Chem. 2015 Apr 8. pii: jbc.M115.646307. PMID:25855791 doi:http://dx.doi.org/10.1074/jbc.M115.646307
5. ↑ de Paula Michelatto D, Karlsson L, Lusa AL, Silva CD, Östberg LJ, Persson B, Guerra-Júnior G, de Lemos-Marini SH, Barbaro M, de Mello MP, Lajic S. Functional and Structural Consequences of Nine CYP21A2 Mutations Ranging from Very Mild to Severe Effects. Int J Endocrinol. 2016;2016:4209670. PMID:27721825 doi:10.1155/2016/4209670
6. ↑ Pallan PS, Wang C, Lei L, Yoshimoto FK, Auchus RJ, Waterman MR, Guengerich FP, Egli M. Human Cytochrome P450 21A2, the Major Steroid 21-Hydroxylase: Structure of the Enzyme-Progesterone Substrate Complex and Rate-Limiting C-H Bond Cleavage. J Biol Chem. 2015 Apr 8. pii: jbc.M115.646307. PMID:25855791 doi:http://dx.doi.org/10.1074/jbc.M115.646307