6FTV

X-ray structure of human heavy chain ferritin in complex with NAMI A

Summary for 6FTV

• Entry DOI: 10.2210/pdb6ftv/pdb
• Descriptor: Ferritin heavy chain, CHLORIDE ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: metallodrug-protein, ferritin, ferroxidase activity, ruthenium, antimetastatic, anticancer agent, transport protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 21692.44

Authors

Merlino, A.,Ferraro, G. (deposition date: 2018-02-23, release date: 2018-08-15, Last modification date: 2024-01-17)

Primary citation

Ciambellotti, S.,Pratesi, A.,Severi, M.,Ferraro, G.,Alessio, E.,Merlino, A.,Messori, L.
The NAMI A - human ferritin system: a biophysical characterization.
Dalton Trans, 47:11429-11437, 2018

PubMed Abstract: The 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 Å 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.

PubMed: 30063237
DOI: 10.1039/c8dt00860d

Experimental method

X-RAY DIFFRACTION (1.58 Å)