| Autor: |
Garstka K; Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland. magdalena.rowinska-zyrek@chem.uni.wroc.pl., Potoczniak G; Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland. magdalena.rowinska-zyrek@chem.uni.wroc.pl., Kozłowski H; Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland. magdalena.rowinska-zyrek@chem.uni.wroc.pl.; Institute of Health Sciences, University of Opole, Katowicka 68 St., 45-060 Opole, Poland., Rowińska-Żyrek M; Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland. magdalena.rowinska-zyrek@chem.uni.wroc.pl. |
| Abstrakt: |
Aspergillus fumigatus is an opportunistic pathogen that is able to invade and grow in the lungs of immunosuppressed patients and cause invasive pulmonary aspergillosis. The concentration of free Zn(II) in living tissues is much lower than that required for optimal fungal growth; thus, to obtain Zn(II) from the host, Aspergillus fumigatus uses highly specified Zn(II) transporters: ZrfA, ZrfB and ZrfC. The ZrfC transporter plays the main role in Zn(II) acquisition from the host in neutral and mildly alkaline environment via interacting with the secreted Aspf2 zincophore. Understanding the Aspf2-ZrfC interactions is therefore necessary for explaining the process of Zn(II) acquisition by Aspergillus fumigatus , and identifying Zn(II) binding sites in its transporter and describing the thermodynamics of such binding are the fundamental steps to achieve this goal. We focus on two probable ZrfC Zn(II) binding sites and show that the Ac-MNCHFHAGVEHCIGAGESESGSSQ-NH 2 region binds Zn(II) with higher affinity than the Ac-TGCHSHGS-NH 2 one and that this binding is much stronger than the binding of Zn(II) to the Aspf2 zincophore, allowing efficient Zn(II) transport from the Aspf2 zincophore to the ZrfC transporter. The same ZrfC fragments also able to bind Ni(II), another metal ion essential for fungi that could also compete with Zn(II) binding, with comparable affinity. |
