6ftv
X-ray structure of human heavy chain ferritin in complex with NAMI AX-ray structure of human heavy chain ferritin in complex with NAMI A
Structural highlights
Function[FRIH_HUMAN] Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity). Publication Abstract from PubMedThe reaction of the antimetastatic ruthenium(iii) drug NAMI A with human H-chain ferritin (HuHf) was investigated through a variety of biophysical methods. We observed that the addition of HuHf to NAMI A solutions significantly increases the rate of spontaneous NAMI A hydrolysis suggesting the occurrence of a direct metallodrug-protein interaction. The resulting hydrolyzed Ru species binds the protein mostly forming a relatively tight 1 : 1 ruthenium/ferritin (subunit) adduct that was then separated and characterized. Notably, this adduct shows a characteristic CD spectrum in the visible region, which is diagnostic of the existence of at least one protein bound ruthenium center. The crystal structure of this NAMI A/HuHf adduct was subsequently solved at 1.58 A resolution; clear evidence is given for the selective binding of a single Ru ion to His105 of each subunit with concomitant release of all other original Ru ligands in agreement with previous observations. We also noted that NAMI A produces a partial inhibition of HuHf ferroxidase activity. The implications of the above results are discussed. The NAMI A - human ferritin system: a biophysical characterization.,Ciambellotti S, Pratesi A, Severi M, Ferraro G, Alessio E, Merlino A, Messori L Dalton Trans. 2018 Jul 31. doi: 10.1039/c8dt00860d. PMID:30063237[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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