3h0t
Hepcidin-Fab complex
Structural highlights
DiseaseHEPC_HUMAN Defects in HAMP are the cause of hemochromatosis type 2B (HFE2B) [MIM:613313; also known as juvenile hemochromatosis (JH). HFE2B is a disorder of iron metabolism with excess deposition of iron in the tissues, bronze skin pigmentation, hepatic cirrhosis, arthropathy and diabetes. The most common symptoms of hemochromatosis type 2 at presentation are hypogonadism and cardiomyopathy.[1] [2] [3] [4] [5] FunctionHEPC_HUMAN Seems to act as a signaling molecule involved in the maintenance of iron homeostasis. Seems to be required in conjunction with HFE to regulate both intestinal iron absorption and iron storage in macrophages (By similarity).[6] Has strong antimicrobial activity against E.coli ML35P N.cinerea and weaker against S.epidermidis, S.aureus and group b streptococcus bacteria. Active against the fungus C.albicans. No activity against P.aeruginosa.[7] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHepcidin is a tightly folded 25-residue peptide hormone containing four disulfide bonds, which has been shown to act as the principal regulator of iron homeostasis in vertebrates. We used multiple techniques to demonstrate a disulfide bonding pattern for hepcidin different from that previously published. All techniques confirmed the following disulfide bond connectivity: Cys(1)-Cys(8), Cys(3)-Cys(6), Cys(2)-Cys(4), and Cys(5)-Cys(7). NMR studies reveal a new model for hepcidin that, at ambient temperatures, interconverts between two different conformations, which could be individually resolved by temperature variation. Using these methods, the solution structure of hepcidin was determined at 325 and 253 K in supercooled water. X-ray analysis of a co-crystal with Fab appeared to stabilize a hepcidin conformation similar to the high temperature NMR structure. Hepcidin revisited, disulfide connectivity, dynamics, and structure.,Jordan JB, Poppe L, Haniu M, Arvedson T, Syed R, Li V, Kohno H, Kim H, Schnier PD, Harvey TS, Miranda LP, Cheetham J, Sasu BJ J Biol Chem. 2009 Sep 4;284(36):24155-67. Epub 2009 Jun 24. PMID:19553669[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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