Structural evidences for a secondary gold binding site in the hydrophobic box of lysozyme

Ferraro, Giarita; Massai, Lara; Messori, Luigi; Cinellu, Maria Agostina; Merlino, Antonello

doi:10.1007/s10534-015-9863-7

Cited by 15 publications

(12 citation statements)

References 43 publications

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“…Thus, the two investigative approaches, applied independently, again provided a very consistent and exhaustive picture for adduct formation. Similar results were obtained using other gold(III) compounds, belonging to the same series, and under different experimental conditions, and even using gold(I) compounds …”

Section: A Joint Esi Ms and Xrd Strategy: Some Relevant Examplessupporting

confidence: 86%

“…The second ligand of the linear gold(I) center is invariantly ac hloride ion, particularly abundant in the specific crystallization buffer. [16] Thus,t he two investigative approaches, appliedi ndependently,a gainp rovided av ery consistent and exhaustive picture for adduct formation.S imilar results were obtained using other gold(III) compounds, belonging to the same series, [17] and under different experimental conditions, [18] and even using gold(I) compounds. [16] Thus, through the above examples, we have demonstrated the feasibility and effectiveness of the proposed hyphenated approach.…”

Section: Aj Oint Esi Ms and Xrd Strategy: Some Relevant Examplessupporting

confidence: 54%

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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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Section: A Joint Esi Ms and Xrd Strategy: Some Relevant Examplessupporting

confidence: 86%

Section: Aj Oint Esi Ms and Xrd Strategy: Some Relevant Examplessupporting

confidence: 54%

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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“…However, it was previously demonstrated by X-ray crystallography that Au(I) ions can coordinate solvent exposed His [50][51][52][53] , also in the presence of free thiols. It has been also shown that Au(I) can bind also Gln side chains, although with lower affinity than that exhibited for Cys, Met and His residues 54 .…”

Section: Reaction Between the Gold N-heterocyclic Carbene Compound Aumentioning

confidence: 99%

First Crystal Structure for a Gold Carbene–Protein Adduct

2016

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The X-ray structure of the adduct formed in the reaction between the gold N-heterocyclic carbene compound Au(NHC)Cl (with NHC = 1-butyl-3-methyl-imidazole-2-ylidene) and the model protein thaumatin is reported here. The structure reveals binding of Au(NHC)(+) fragments to distinct protein sites. Notably, binding of the gold compound occurs at lysine side chains and at the N-terminal tail; the metal binds the protein after releasing Cl(-) ligand, but retaining NHC fragment.

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“…Indeed, metal ion Au(I) is a soft metal center, demonstrating a strongly pronounced affinity toward soft ligands such as thiols of cysteines and thioethers of methionines [15] and even more with selenols of selenocysteine residues [16]. Nevertheless, several X-ray crystallographic studies proved that Au(I) ions are able to bind solvent-exposed His [17,18] even when free thiols are available. Moreover, Au(I) complexes may bind the Arg and Lys side chains as well as the N-terminal of Ala [19], albeit in the absence of available cysteines, methionines, and histidines.…”

Section: Computational Studies Of Au(i) Metallodrugsmentioning

confidence: 99%

Computational Studies of Au(I) and Au(III) Anticancer MetalLodrugs: A Survey

et al. 2021

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Owing to the growing hardware capabilities and the enhancing efficacy of computational methodologies, computational chemistry approaches have constantly become more important in the development of novel anticancer metallodrugs. Besides traditional Pt-based drugs, inorganic and organometallic complexes of other transition metals are showing increasing potential in the treatment of cancer. Among them, Au(I)- and Au(III)-based compounds are promising candidates due to the strong affinity of Au(I) cations to cysteine and selenocysteine side chains of the protein residues and to Au(III) complexes being more labile and prone to the reduction to either Au(I) or Au(0) in the physiological milieu. A correct prediction of metal complexes’ properties and of their bonding interactions with potential ligands requires QM computations, usually at the ab initio or DFT level. However, MM, MD, and docking approaches can also give useful information on their binding site on large biomolecular targets, such as proteins or DNA, provided a careful parametrization of the metal force field is employed. In this review, we provide an overview of the recent computational studies of Au(I) and Au(III) antitumor compounds and of their interactions with biomolecular targets, such as sulfur- and selenium-containing enzymes, like glutathione reductases, glutathione peroxidase, glutathione-S-transferase, cysteine protease, thioredoxin reductase and poly (ADP-ribose) polymerase 1.

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Structural evidences for a secondary gold binding site in the hydrophobic box of lysozyme

Cited by 15 publications

References 43 publications

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

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

First Crystal Structure for a Gold Carbene–Protein Adduct

Computational Studies of Au(I) and Au(III) Anticancer MetalLodrugs: A Survey

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