| Structural highlights
Function
[CYBR1_HUMAN] Ferric-chelate reductase that reduces Fe(3+) to Fe(2+). Present at the brush border of duodenal enterocytes where it probably reduces dietary Fe(3+) thereby facilitating its transport into the mucosal cells. Uses ascorbate as electron donor. May be involved in extracellular ascorbate recycling in erythrocyte membranes. May also act as a ferrireductase in airway epithelial cells.[1] [2] [3] [4]
Publication Abstract from PubMed
Dietary iron absorption is regulated by duodenal cytochrome b (Dcytb), an integral membrane protein that catalyzes reduction of nonheme Fe(3+) by electron transfer from ascorbate across the membrane. This step is essential to enable iron uptake by the divalent metal transporter. Here we report the crystallographic structures of human Dcytb and its complex with ascorbate and Zn(2+). Each monomer of the homodimeric protein possesses cytoplasmic and apical heme groups, as well as cytoplasmic and apical ascorbate-binding sites located adjacent to each heme. Zn(2+) coordinates to two hydroxyl groups of the apical ascorbate and to a histidine residue. Biochemical analysis indicates that Fe(3+) competes with Zn(2+) for this binding site. These results provide a structural basis for the mechanism by which Fe(3+) uptake is promoted by reducing agents and should facilitate structure-based development of improved agents for absorption of orally administered iron.
Structural basis for promotion of duodenal iron absorption by enteric ferric reductase with ascorbate.,Ganasen M, Togashi H, Takeda H, Asakura H, Tosha T, Yamashita K, Hirata K, Nariai Y, Urano T, Yuan X, Hamza I, Mauk AG, Shiro Y, Sugimoto H, Sawai H Commun Biol. 2018 Aug 17;1:120. doi: 10.1038/s42003-018-0121-8. eCollection 2018. PMID:30272000[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zaahl MG, Merryweather-Clarke AT, Kotze MJ, van der Merwe S, Warnich L, Robson KJ. Gene symbol: DCYTB/CYBRD1. Disease: primary iron overload. Hum Genet. 2005 Dec;118(3-4):548-9. PMID:16521311
- ↑ Zaahl MG, Merryweather-Clarke AT, Kotze MJ, van der Merwe S, Warnich L, Robson KJ. Gene symbol: DCYTB/CYBRD1. Disease: primary iron overload. Hum Genet. 2005 Dec;118(3-4):549. PMID:16521312
- ↑ Su D, May JM, Koury MJ, Asard H. Human erythrocyte membranes contain a cytochrome b561 that may be involved in extracellular ascorbate recycling. J Biol Chem. 2006 Dec 29;281(52):39852-9. Epub 2006 Oct 26. PMID:17068337 doi:http://dx.doi.org/M606543200
- ↑ Constantine CC, Anderson GJ, Vulpe CD, McLaren CE, Bahlo M, Yeap HL, Gertig DM, Osborne NJ, Bertalli NA, Beckman KB, Chen V, Matak P, McKie AT, Delatycki MB, Olynyk JK, English DR, Southey MC, Giles GG, Hopper JL, Allen KJ, Gurrin LC. A novel association between a SNP in CYBRD1 and serum ferritin levels in a cohort study of HFE hereditary haemochromatosis. Br J Haematol. 2009 Oct;147(1):140-9. doi: 10.1111/j.1365-2141.2009.07843.x. Epub, 2009 Aug 10. PMID:19673882 doi:http://dx.doi.org/10.1111/j.1365-2141.2009.07843.x
- ↑ Ganasen M, Togashi H, Takeda H, Asakura H, Tosha T, Yamashita K, Hirata K, Nariai Y, Urano T, Yuan X, Hamza I, Mauk AG, Shiro Y, Sugimoto H, Sawai H. Structural basis for promotion of duodenal iron absorption by enteric ferric reductase with ascorbate. Commun Biol. 2018 Aug 17;1:120. doi: 10.1038/s42003-018-0121-8. eCollection 2018. PMID:30272000 doi:http://dx.doi.org/10.1038/s42003-018-0121-8
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