The binding of platinum complexes to tuna cytochrome <i>c</i>

Boswell, A P; Moore, Geoffrey R.; Williams, R. J. P.

doi:10.1042/bj2010523

Cited by 9 publications

(2 citation statements)

References 8 publications

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“…The first step most likely involves reaction between the sulfur of Met1 and K 2 PtCl 4 in which the sulfur becomes a ligand to Pt(II) after displacement of one of the four chlorine ligands. There is ample precedent for this type of interaction with methionine as well as methionyl residues in proteins (33,34,41,(45)(46)(47)(48). Following the formation of this initial monoadduct of platinum {i.e., [Pt(Cl 3 )(M1-S)]; M r ) 18 126 Da}, a total of three additional functional groups (one of which is probably the R-NH 2 group of Met1) in the vicinity of the newly formed Pt(II)-protein sulfonium adduct also appear to become ligands to platinum, each successively displacing the remaining three chlorine atoms and forming the di-, tri-, and tetraprotein adducts (M r ) 18 090, 18 053, and 18 017 Da, respectively) with Pt(II) (Scheme 1).…”

Section: Discussionmentioning

confidence: 99%

Elucidation of Solvent Exposure, Side-Chain Reactivity, and Steric Demands of the Trifluoromethionine Residue in a Recombinant Protein

et al. 2001

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When incorporated into proteins, fluorinated amino acids have been utilized as 19F NMR probes of protein structure and protein-ligand interactions, and as subtle structural replacements for their parent amino acids which is not possible using the standard 20-amino acid repertoire. Recent investigations have shown the ability of various fluorinated methionines, such as difluoromethionine (DFM) and trifluoromethionine (TFM), to be bioincorporated into recombinant proteins and to be extremely useful as 19F NMR biophysical probes. Interestingly, in the case of the bacteriophage lambda lysozyme (LaL) which contains only three Met residues (at positions 1, 14, and 107), four 19F NMR resonances are observed when TFM is incorporated into LaL. To elucidate the underlying structural reasons for this anomalous observation and to more fully explore the effect of TFM on protein structure, site-directed mutagenesis was used to assign each 19F NMR resonance. Incorporation of TFM into the M14L mutant resulted in the collapse of the two 19F resonances associated with TFM at position 107 into a single resonance, suggesting that when position 14 in wild-type protein contains TFM, a subtle but different environment exists for the methionine at position 107. In addition, 19F and [1H-13C]-HMQC NMR experiments have been utilized with paramagnetic line broadening and K2PtCl4 reactivity experiments to obtain information about the probable spatial position of each Met in the protein. These results are compared with the recently determined crystal structure of LaL and allow for a more detailed structural explanation for the effect of fluorination on protein structure.

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Section: Discussionmentioning

confidence: 99%

Elucidation of Solvent Exposure, Side-Chain Reactivity, and Steric Demands of the Trifluoromethionine Residue in a Recombinant Protein

et al. 2001

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“…[42][43][44][45] Interactions of Pt(II) drugs with other model proteins (cytochrome c, superoxide dismutase, lysozyme, myoglobin), or mixtures of them, were further investigated, also by one of us, by various techniques including MS, NMR, ICP-OES and X-ray crystallography to provide a description of the system at a molecular level. [46][47][48][49][50][51][52][53][54] Fig. 2 depicts the global X-ray structure of cisplatin bound to hen egg white lysozyme (HEWL, PDB 2I67).…”

Section: Anticancer Platinum Compounds and Initial Studies Of Their Imentioning

confidence: 99%

Interactions of anticancer Pt compounds with proteins: an overlooked topic in medicinal inorganic chemistry?

2012

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Mitochondria as a critical target of the chemotheraputic agent cisplatin in head and neck cancer

Cullen,

Yang,

Schumaker

et al. 2007

J Bioenerg Biomembr

170

129

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Cisplatin is among the most important chemotherapeutic agents ever developed. It is a critical component of therapeutic regimens in a broad range of malignancies. However, more than a generation after its clinical introduction, the exact mechanism of cisplatin action on tumor cells is not fully defined. The preponderance of research over the last three decades has focused on cisplatin interactions with nuclear DNA which are felt to lead to apoptotic cell death in sensitive cells. However, recent data have shown that cisplatin may have important direct interactions with mitochondria which can induce apoptosis and may account for a significant portion of the clinical activity associated with this drug. These direct interactions between cisplatin and mitochondria may have critical implications for our understanding of this class of drugs and the development of new therapeutic agents.

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The binding of platinum complexes to tuna cytochrome c

Abstract: The binding of [PtCl4]2- and cis-[PtCl2(NH3)2] to methionine-65 of tuna cytochrome c was investigated by 1H n.m.r. The modification at methionine-65 is shown to cause an extremely small structural perturbation to the protein at the site of modification.

Cited by 9 publications

References 8 publications

Elucidation of Solvent Exposure, Side-Chain Reactivity, and Steric Demands of the Trifluoromethionine Residue in a Recombinant Protein

Elucidation of Solvent Exposure, Side-Chain Reactivity, and Steric Demands of the Trifluoromethionine Residue in a Recombinant Protein

Interactions of anticancer Pt compounds with proteins: an overlooked topic in medicinal inorganic chemistry?

Mitochondria as a critical target of the chemotheraputic agent cisplatin in head and neck cancer

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