The crystal structure analysis of the relative binding of cisplatin and carboplatin in a mixture with histidine in a protein studied at 100 and 300 K with repeated X-ray irradiation

Helliwell, John R.; Tanley, S.W.M.

doi:10.1107/s090744491204423x

Cited by 35 publications

(15 citation statements)

References 21 publications

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“…Might this arise from X-ray absorbed dose effects? In a previous study, 18 we showed that cisplatin binding was stable up to a dose of 1.7 MGy. The total absorbed X-ray doses of each dataset at the three temperatures in this study were 0.31 MGy, 0.37 Mgy, 0.48 MGy, and 0.31 MGy (Table I and Table S1 31 ), and show that the cisplatin and carboplatin should be stable at these absorbed X-ray doses.…”

Section: Discussionmentioning

confidence: 76%

Structural dynamics of cisplatin binding to histidine in a protein

Tanley

Helliwell

2014

Structural Dynamics

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The platinum anti-cancer agents cisplatin and carboplatin bind to the histidine 15 residue in the model protein hen egg white lysozyme. By using temperatures either side of the protein glass transition state (∼180 K), several platinum binding modes are seen and show that not all these platinum modes are stable. In particular, the mean square displacement vibration amplitudes of the cisplatin and of the histidine to which it is bound are analysed in detail. As well as the multiple platinum peaks, the electron density for the His-15 side chain is weak to absent at 150 K and 200 K, which points to the imidazole ring of the His side chain sampling multiple positions. Most interestingly, the His-15 imidazole becomes more ordered at room temperature.

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Section: Discussionmentioning

confidence: 76%

Structural dynamics of cisplatin binding to histidine in a protein

Tanley

Helliwell

2014

Structural Dynamics

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“…6B), and the mass spectrometry results are shown in Table 1. The histidine content in each identified protein is also included in Table 1, since recent reports suggest that histidine residues in a protein contribute to cisplatin binding [35], [36]. While most of the proteins have low histidine contents, higher levels in casein kinase II and eukaryotic translation initiation factor 3 may contribute to binding of these proteins to cisplatin.…”

Section: Resultsmentioning

confidence: 99%

Identification of Cisplatin-Binding Proteins Using Agarose Conjugates of Platinum Compounds

et al. 2013

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Cisplatin is widely used as an antineoplastic drug, but its ototoxic and nephrotoxic side-effects, as well as the inherent or acquired resistance of some cancers to cisplatin, remain significant clinical problems. Cisplatin's selectivity in killing rapidly proliferating cancer cells is largely dependent on covalent binding to DNA via cisplatin's chloride sites that had been aquated. We hypothesized that cisplatin's toxicity in slowly proliferating or terminally differentiated cells is primarily due to drug-protein interactions, instead of drug-DNA binding. To identify proteins that bind to cisplatin, we synthesized two different platinum-agarose conjugates, one with two amino groups and another with two chlorides attached to platinum that are available for protein binding, and conducted pull-down assays using cochlear and kidney cells. Mass spectrometric analysis on protein bands after gel electrophoresis and Coomassie blue staining identified several proteins, including myosin IIA, glucose-regulated protein 94 (GRP94), heat shock protein 90 (HSP90), calreticulin, valosin containing protein (VCP), and ribosomal protein L5, as cisplatin-binding proteins. Future studies on the interaction of these proteins with cisplatin will elucidate whether these drug-protein interactions are involved in ototoxicity and nephrotoxicity, or contribute to tumor sensitivity or resistance to cisplatin treatment.

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“…35 However, our structures cannot be directly compared with that obtained for HEWL/carboplatin + cisplatin, 35 since the bis-adduct has not been obtained using the same procedure by Helliwell and Tanley. 35 However, our structures cannot be directly compared with that obtained for HEWL/carboplatin + cisplatin, 35 since the bis-adduct has not been obtained using the same procedure by Helliwell and Tanley.…”

Section: Crystallographymentioning

confidence: 99%

Oxaliplatin vs. cisplatin: competition experiments on their binding to lysozyme

et al. 2015

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The model protein hen egg white lysozyme was challenged with oxaliplatin and cisplatin. ESI mass spectrometry, surface plasmon resonance and thermal shift analyses demonstrate the formation of a bis-platinum adduct, though in very small amounts. Crystals of the bis-platinum adduct were obtained using two different preparations and the X-ray structures were solved at 1.85 Å and 1.95 Å resolution. Overall, the obtained data point out that, under the analyzed conditions, the two Pt drugs have similar affinities for the protein, but bind on its surface at two non-overlapping sites. In other words, these two drugs manifest a significantly different reactivity with this model protein and do not compete for the same protein binding sites.

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The crystal structure analysis of the relative binding of cisplatin and carboplatin in a mixture with histidine in a protein studied at 100 and 300 K with repeated X-ray irradiation

Cited by 35 publications

References 21 publications

Structural dynamics of cisplatin binding to histidine in a protein

Structural dynamics of cisplatin binding to histidine in a protein

Identification of Cisplatin-Binding Proteins Using Agarose Conjugates of Platinum Compounds

Oxaliplatin vs. cisplatin: competition experiments on their binding to lysozyme

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