5NJ7
The X-ray structure of the adduct formed in the reaction between bovine pancreatic ribonuclease and arsenoplatin-1
Summary for 5NJ7
| Entry DOI | 10.2210/pdb5nj7/pdb |
| Descriptor | Ribonuclease pancreatic, arsenoplatin-1 (3 entities in total) |
| Functional Keywords | ribonuclease, arsenoplatin, metal based drugs, hydrolase |
| Biological source | Bos taurus (Bovine) |
| Total number of polymer chains | 2 |
| Total formula weight | 29089.12 |
| Authors | Ferraro, G.,Merlino, A. (deposition date: 2017-03-28, release date: 2018-05-16, Last modification date: 2024-11-06) |
| Primary citation | Miodragovic, D.,Merlino, A.,Swindell, E.P.,Bogachkov, A.,Ahn, R.W.,Abuhadba, S.,Ferraro, G.,Marzo, T.,Mazar, A.P.,Messori, L.,O'Halloran, T.V. Arsenoplatin-1 Is a Dual Pharmacophore Anticancer Agent. J.Am.Chem.Soc., 141:6453-6457, 2019 Cited by PubMed Abstract: Arsenoplatins are adducts of two chemically important anticancer drugs, cisplatin and arsenic trioxide, that have a Pt(II) bond to an As(III) hydroxide center. Screens of the NCI-60 human tumor cell lines reveal that arsenoplatin-1 (AP-1), [Pt(μ-NHC(CH)O)ClAs(OH)], the first representative of this novel class of anticancer agents, displays a superior activity profile relative to the parent drugs AsO or cisplatin in a majority of cancer cell lines tested. These activity profiles are important because the success of arsenic trioxide in blood cancers (such as APL) has not been seen in solid tumors due to the rapid clearance of arsenous acid from the body. To understand the biological chemistry of these compounds, we evaluated interactions of AP-1 with the two important classes of biomolecules-proteins and DNA. The first structural studies of AP-1 bound to model proteins reveal that platinum(II) binds the Nε of His in a manner that preserves the Pt-As bond. We find that AP-1 readily enters cells and binds to DNA with an intact Pt-As bond (Pt:As ratio of 1). At longer incubation times, however, the Pt:As ratio in DNA samples increases, suggesting that the Pt-As bond breaks and releases the As(OH) moiety. We conclude that arsenoplatin-1 has the potential to deliver both Pt and As species to a variety of hematological and solid cancers. PubMed: 30943017DOI: 10.1021/jacs.8b13681 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.15 Å) |
Structure validation
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