title: Interactions of the organogold(III) compound Aubipyc with the copper chaperone Atox1: a joint mass spectrometry and circular dichroism investigation.
abstract: The so called "copper trafficking system" in mammalian cells is primarily devoted to the regulation of copper transport and homeostasis. This system, now well characterized, consists of a few strictly interconnected proteins that assist copper entrance inside cells and then promote metal transfer and delivery to essential copper-dependent cellular proteins (Boal and Rosenzweig 2009a; Banci et al., Mol Life Sci 67:2563-2589, 2010). Yet, the "copper trafficking system" may also facilitate the entrance inside cells of non-physiological metal species such as clinically established platinum drugs. ESI and MALDI MS methods are exploited here to characterize the interactions occurring between the experimental anticancer organogold(III) drug, Aubipyc, and the copper chaperone Atox1, a key protein of the copper trafficking system. The nature of the adducts that are formed when reacting Aubipyc with Atox1 is elucidated in detail. Characterization of the Aubipyc/Atox1 system is further supported by circular dichroism experiments. Binding competitions with mercury and bismuth ions were also explored. The relevance and the biological implications of the present results are discussed.
authors.affiliation: MetMed, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Marzo
authors.affiliation: MetMed, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Scaletti
authors.affiliation: Mass Spectrometry Center (CISM), University of Florence, via U. Schiff 6, 50019, Sesto Fiorentino, FI, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Michelucci
authors.affiliation: Department of Chemistry and Industrial Chemistry, University of Pisa, Via Moruzzi 13, 56124, Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Gabbiani
authors.affiliation: Department of Chemistry and Industrial Chemistry, University of Pisa, Via Moruzzi 13, 56124, Pisa, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Pescitelli
authors.affiliation: MetMed, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy. luigi.messori@unifi.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
authors.affiliation: MetMed, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy. lara.massai@unifi.it.
authors.forename: Lara
authors.initials: L
authors.lastname: Massai
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry*; D001692:Biological Transport; D001729:Bismuth / Q000737:chemistry; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry; D000079922:Copper Transport Proteins; D006801:Humans; D007700:Kinetics; D008628:Mercury / Q000737:chemistry; D056511:Metallochaperones / Q000737:chemistry*; D018832:Molecular Chaperones; D050607:Organogold Compounds / Q000737:chemistry*; D011485:Protein Binding; D012996:Solutions; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013816:Thermodynamics
chemical_list: C474500:ATOX1 protein, human; D000970:Antineoplastic Agents; D000079922:Copper Transport Proteins; D056511:Metallochaperones; D018832:Molecular Chaperones; D050607:Organogold Compounds; D012996:Solutions; C453480:hydroxo(6-(1,1-dimethylbenzyl)-2,2'-bipyridine)gold(III); D015082:2,2'-Dipyridyl; D003300:Copper; D008628:Mercury; D001729:Bismuth
keywords: Anticancer drugs; Circular dichroism; ESI-MS; Gold compounds; Protein melting; Protein metalation