Platinated oligomers of bovine pancreatic ribonuclease: Structure and stability

Picone, Delia; Donnarumma, Federica; Ferraro, Giarita; Krauss, Irene Russo; Fagagnini, Andrea; Gotte, Giovanni; Merlino, Antonello

doi:10.1016/j.jinorgbio.2015.02.011

Cited by 25 publications

(18 citation statements)

References 41 publications

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“…On the other hand, these data also agree with previous crystallographic findings on the adduct formed in the reaction between trans-Pt derivatives and RNase A [26]. It should be also noted that cisplatin has been found to bind both His105 and His119 in RNase A-cisplatin crystals of a different space group and obtained under different crystallization conditions [25]. In this respect, we cannot exclude that carboplatin could be able to bind His105 and His119, using the approach described in Ref.…”

Section: Discussionsupporting

confidence: 90%

“…In this respect, we cannot exclude that carboplatin could be able to bind His105 and His119, using the approach described in Ref. [25] or after longer soaking time.…”

Section: Discussionmentioning

confidence: 99%

“…2A). An additional structure for RNase Acisplatin adduct (space group P3 2 21), obtained upon crystallizing purified protein after 24 h of incubation in the presence of a large excess of cisplatin, shows that additional binding sites can be observed close to His105 and His119 [25].…”

Section: Introductionmentioning

confidence: 99%

“…RNase A was chosen as a model to study protein interactions with Pt-based [15,20,25,26] and other metal drugs [27,28], since it is a stable, small, well characterized protein that is commercially available at low cost; in addition, it is easy to crystallize, forming crystals resistant to soaking under different experimental conditions. This protein is frequently used as a model system also in many other fields, including protein chemistry, enzymology, chemical synthesis and structural biology [29].…”

Section: Introductionmentioning

confidence: 99%

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Interactions of carboplatin and oxaliplatin with proteins: Insights from X-ray structures and mass spectrometry studies of their ribonuclease A adducts

Messori

Marzo

Merlino

2015

Journal of Inorganic Biochemistry

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Oxaliplatin and carboplatin are two platinum(II) drugs in widespread clinical use for the treatment of various types of cancers; yet, structural information on their interactions with proteins is scarce. Here, the X-ray structures of the adducts formed upon reaction of carboplatin and oxaliplatin with bovine pancreatic ribonuclease (RNase A) are reported and compared with results obtained for the structure of the RNase A-cisplatin adduct derived from isomorphous crystals, under the same experimental conditions. Additional details on the binding mode of these metallodrugs toward RNase A are provided by electrospray ionization mass spectrometry (ESI MS) measurements, thus offering insight on the occurring metal-protein interactions. Notably, while carboplatin and cisplatin mainly bind the side chain of Met29, oxaliplatin also binds the side chains of Asp14, of catalytically important His119 and, to a lesser extent, of His105. On the basis of the available data, a likely mechanism for oxaliplatin hydrolysis and binding to the protein is proposed. These results are potentially useful for a better understanding of the biological chemistry, toxicity and side effects of this important class of antitumor agents.

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Section: Discussionsupporting

confidence: 90%

“…In this respect, we cannot exclude that carboplatin could be able to bind His105 and His119, using the approach described in Ref. [25] or after longer soaking time.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Interactions of carboplatin and oxaliplatin with proteins: Insights from X-ray structures and mass spectrometry studies of their ribonuclease A adducts

Messori

Marzo

Merlino

2015

Journal of Inorganic Biochemistry

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“…The structure has been deposited in the Cambridge Crystallographic Data Centre under the accession code 1476883. 20 The antiproliferative activity of Compound 1 was evaluated by the MTT assay towards different cell lines, including the cancer cell lines SKOV-3 (human ovarian cancer), A2780 (human ovarian carcinoma) and A549 cells (human lung carcinoma) and cisplatin resistant cancer cells A2780cis and 25 SKOV-3cis. Data were compared with those obtained using L or cisplatin and testing the compound against non-cancerous cell lines (Table 1).…”

mentioning

confidence: 99%

Unusual mode of protein binding by a cytotoxic π-arene ruthenium(ii) piano-stool compound containing an O,S-chelating ligand

et al. 2016

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A new pseudo-octahedral π-arene ruthenium(ii) piano-stool compound, containing an O,S-bidentate ligand (compound 1) and showing significant cytotoxic activity in vitro, was synthesized and characterized. In solution stability and interaction with the model protein bovine pancreatic ribonuclease (RNase A) were investigated by using UV-Vis absorption spectroscopy. Its crystal structure and that of the adduct formed upon reaction with RNase A were obtained by X-ray crystallography. The comparison between the structure of purified compound 1 and that of the fragment bound to RNase A reveals an unusual mode of protein binding that includes ligand exchange and alteration of coordination sphere geometry.

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Protein Metalation by Anticancer Metallodrugs: A Joint ESI MS and XRD Investigative Strategy

Merlino

Marzo

Messori

2017

Chemistry A European J

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Interactions of metal-based drugs with proteins and consequent adduct formation (the so-called "protein metalation" process) play a key role in the mode of action of several anticancer agents and in determining their toxicological profile. Through a novel investigative strategy grounded on the combined use of electrospray ionization mass spectrometry (ESI MS) and biological macromolecule X-ray crystallography we show that it is possible to clarify in depth the metalation process of small model proteins; a number of instructive examples are provided. Recently, this kind of investigative approach has been extended to bigger proteins such as human serum albumin and horse spleen ferritin, with rather encouraging results. Overall, by application of this strategy, metalation of proteins caused by anticancer metallodrugs can be disclosed in the molecular detail.

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Platinated oligomers of bovine pancreatic ribonuclease: Structure and stability

Cited by 25 publications

References 41 publications

Interactions of carboplatin and oxaliplatin with proteins: Insights from X-ray structures and mass spectrometry studies of their ribonuclease A adducts

Interactions of carboplatin and oxaliplatin with proteins: Insights from X-ray structures and mass spectrometry studies of their ribonuclease A adducts

Unusual mode of protein binding by a cytotoxic π-arene ruthenium(ii) piano-stool compound containing an O,S-chelating ligand

Protein Metalation by Anticancer Metallodrugs: A Joint ESI MS and XRD Investigative Strategy

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