The necessity of new antifungal agents is unarguable, since current therapeutic treatments are not always effective due to the development of drug resistance. Nevertheless, the assimilation of metal nutrients from the host environment is a fundamental aspect of infections and deeper insights into the mechanism of metal uptake and transport in fungal species can provide crucial information to design new antifungal drugs [1]. From this perspective, we recently studied Zn(II) and Cu(II) binding behavior towards C4YJH2, a protein sequence of 199 amino acid residues, found in the genome of Candida albicans. Our previous work has confirmed that the main histidine-rich sequences between 131-148 (FHEHGHSHSHG SGGGGGG) and 157-165 (SHSHSHSHS) residues are involved in metal coordination [2]. In the native protein, the two His-rich domains are linked by the 9-residue sequence GSDHSGDSK, also containing a histidine and thus possibly contributing to the metal binding. Therefore, we decided to extend our investigation focusing on this “linker”. The protected peptide Ac-GSDHSGDSK-NH2 (148-156 residues) has been considered, along with its analogues Ac-GSDHSGASK-NH2, Ac-GADHAGDAK-NH2, Ac-GSDH-NH2, Ac-HSGD-NH2. The preliminary results presented here concern the stoichiometry and thermodynamics of complex-formation of the above reported ligands with Zn(II) and Cu(II), investigated by means of potentiometric titrations; the hypothesized geometry of the formed species is also discussed, on the basis of UV-Vis and circular dichroism data at variable pH. The comparison among the behaviors of the different analogues helps to shed light on the role of specific residues in metal coordination geometry and complex stability. [1] M. Blatzer, J.P. Latgé, Curr. Opin. Microbiol. 40 (2017) 152-159. [2] D. Bellotti, D. Łoboda, M. Rowińska-Żyrek, M. Remelli, New J. Chem. 42 (2018) 8123-8130.

Investigation on Zn(II) and Cu(II) binding sites in C4YJH2, a putative metal transporter of Candida albicans

Denise Bellotti
Primo
;
Maurizio Remelli
Ultimo
2018

Abstract

The necessity of new antifungal agents is unarguable, since current therapeutic treatments are not always effective due to the development of drug resistance. Nevertheless, the assimilation of metal nutrients from the host environment is a fundamental aspect of infections and deeper insights into the mechanism of metal uptake and transport in fungal species can provide crucial information to design new antifungal drugs [1]. From this perspective, we recently studied Zn(II) and Cu(II) binding behavior towards C4YJH2, a protein sequence of 199 amino acid residues, found in the genome of Candida albicans. Our previous work has confirmed that the main histidine-rich sequences between 131-148 (FHEHGHSHSHG SGGGGGG) and 157-165 (SHSHSHSHS) residues are involved in metal coordination [2]. In the native protein, the two His-rich domains are linked by the 9-residue sequence GSDHSGDSK, also containing a histidine and thus possibly contributing to the metal binding. Therefore, we decided to extend our investigation focusing on this “linker”. The protected peptide Ac-GSDHSGDSK-NH2 (148-156 residues) has been considered, along with its analogues Ac-GSDHSGASK-NH2, Ac-GADHAGDAK-NH2, Ac-GSDH-NH2, Ac-HSGD-NH2. The preliminary results presented here concern the stoichiometry and thermodynamics of complex-formation of the above reported ligands with Zn(II) and Cu(II), investigated by means of potentiometric titrations; the hypothesized geometry of the formed species is also discussed, on the basis of UV-Vis and circular dichroism data at variable pH. The comparison among the behaviors of the different analogues helps to shed light on the role of specific residues in metal coordination geometry and complex stability. [1] M. Blatzer, J.P. Latgé, Curr. Opin. Microbiol. 40 (2017) 152-159. [2] D. Bellotti, D. Łoboda, M. Rowińska-Żyrek, M. Remelli, New J. Chem. 42 (2018) 8123-8130.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2478994
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact