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Solution structure and novel insights into phylogeny and mode of action of the Neosartorya (Aspergillus) fischeri antifungal protein (NFAP)

Hajdu, Dorottya Zsuzsanna and Huber, Anna and Czajlik, András and Tóth, Liliána and Kele, Zoltán and Kocsubé, Sándor and Fizil, Ádám and Galgóczi, László Norbert and Batta, Gyula (2019) Solution structure and novel insights into phylogeny and mode of action of the Neosartorya (Aspergillus) fischeri antifungal protein (NFAP). INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 129. pp. 511-522. ISSN 0141-8130

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Abstract

Small, cysteine-rich and cationic antifungal proteins from natural sources are promising candidates for the development of novel treatment strategies to prevent and combat infections caused by drug-resistant fungi. However, limited information about their structure and antifungal mechanism hampers their future applications. In the present study, we determined the solution structure, dynamics and associated solvent areas of the Neosartorya (Aspergillus) fischeri antifungal protein NFAP. Genome mining within the genus revealed the presence of orthologous genes in N. fischeri and Neosartorya spathulata, and genes encoding closely related proteins can be found in Penicillium brasiliensis and Penicillium oxalicum. We show that the tertiary structure of these putative proteins can be resolved using the structure of NFAP as reliable template for in silico prediction. Localization studies with fluorescence-labelled protein pointed at an energy-dependent uptake mechanism of NFAP in the sensitive model fungus Neurospora crassa and subsequent cytoplasmic localization coincided with cell-death induction. The presented results contribute to a better understanding of the structure/function relationship of NFAP and related proteins and pave the way towards future antifungal drug development.

Item Type: Article
Uncontrolled Keywords: nuclear magnetic resonance (NMR); Antifungal mechanism; Neosartorya (Aspergillus) fischeri antifungal protein (NFAP);
Subjects: Q Science / természettudomány > QD Chemistry / kémia > QD04 Organic chemistry / szerves kémia
Q Science / természettudomány > QR Microbiology / mikrobiológia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 11 Sep 2019 12:24
Last Modified: 11 Sep 2019 12:24
URI: http://real.mtak.hu/id/eprint/99086

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