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Thermodynamic and spectroscopic study of Cu(II) and Zn(II) complexes with the (148-156) peptide fragment of C4YJH2, a putative metal transporter of Candida albicans

Abstract

Candida albicans is a widespread human pathogen which can infect humans at different levels. As the majority of microorganisms, it needs transition metals as micronutrients for its subsistence. In order to acquire these nutrients from the host, C. albicans employs various strategies, also involving chelating proteins specifically expressed to sequester metals from the environment. A histidine-rich protein sequence identified in C. albicans genome, named C4YJH2, has been recently studied for its putative role in Zn(II) transport. Two outer membrane major histidine-rich clusters of C4YJH2, namely the domains 131-148 (FHEHGHSHSHGSGGGGGG) and 157-165 (SHSHSHSHS), have been confirmed as strong binding sites for the Cu(II) and Zn(II) ions. Nevertheless, the 9-residue “linker” sequence 148-156 (GSDHSGDSK) between the two His-rich fragments of C4YJH2, containing an additional His residue, can also contribute to metal binding. In the present work, the protected peptide Ac-GSDHSGDSK-NH2 and some analogues (Ac-GSDHSGASK-NH2, Ac-GADHAGDAK-NH2, Ac-GSDH-NH2, Ac-HSGD-NH2) have been synthesized and their metal binding properties have been studied in detail. The thermodynamics of complex-formation equilibria of the above reported ligands with Cu(II) and Zn(II) ions have been studied by potentiometry in a wide pH range and the stoichiometry of formed species has been confirmed by mass spectrometry; the most likely solution structures of metal complexes are also discussed on the basis of NMR, UV-Vis, circular dichroism (CD) and EPR data. The results show the importance of Asp7 in the stabilization of Zn(II) complexes and suggest a significant role of the (quite abundant) Ser residues in the task of metal uptake and regulation.

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Publication details

The article was received on 09 Oct 2019, accepted on 08 Nov 2019 and first published on 08 Nov 2019


Article type: Paper
DOI: 10.1039/C9MT00251K
Metallomics, 2019, Accepted Manuscript

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    Thermodynamic and spectroscopic study of Cu(II) and Zn(II) complexes with the (148-156) peptide fragment of C4YJH2, a putative metal transporter of Candida albicans

    D. Bellotti, C. Tocchio, R. Guerrini, M. Rowinska-Zyrek and M. Remelli, Metallomics, 2019, Accepted Manuscript , DOI: 10.1039/C9MT00251K

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