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1.

001-es BibID:BIBFORM090877
035-os BibID:(scopus)85099978064 (wos)000615359000001
Első szerző:Czajlik András (gyógyszerész)
Cím:Solution Structure, Dynamics, and New Antifungal Aspects of the Cysteine-Rich Miniprotein PAFC / András Czajlik, Jeanett Holzknecht, László Galgóczy, Liliána Tóth, Péter Poór, Attila Ördög, Györgyi Váradi, Alexander Kühbacher, Attila Borics, Gábor K. Tóth, Florentine Marx, Gyula Batta
Dátum:2021
ISSN:1661-6596 1422-0067
Megjegyzések:The genome of Penicillium chrysogenum Q176 contains a gene coding for the 88-amino-acid (aa)-long glycine- and cysteine-rich P. chrysogenum antifungal protein C (PAFC). After maturation, the secreted antifungal miniprotein (MP) comprises 64 aa and shares 80% aa identity with the bubble protein (BP) from Penicillium brevicompactum, which has a published X-ray structure. Our team expressed isotope (15N, 13C)-labeled, recombinant PAFC in high yields, which allowed us to determine the solution structure and molecular dynamics by nuclear magnetic resonance (NMR) experiments. The primary structure of PAFC is dominated by 14 glycines, and therefore, whether the four disulfide bonds can stabilize the fold is challenging. Indeed, unlike the few published solution structures of other antifungal MPs from filamentous ascomycetes, the NMR data indicate that PAFC has shorter secondary structure elements and lacks the typical ??-barrel structure, though it has a positively charged cavity and a hydrophobic core around the disulfide bonds. Some parts within the two putative ??-core motifs exhibited enhanced dynamics according to a new disorder index presentation of 15N-NMR relaxation data. Furthermore, we also provided a more detailed insight into the antifungal spectrum of PAFC, with specific emphasis on fungal plant pathogens. Our results suggest that PAFC could be an effective candidate for the development of new antifungal strategies in agriculture.
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Penicillium chrysogenum
antifungal protein PAFC
γ-core motif
solution structure
dynamics
nuclear magnetic resonance
plant protection
Megjelenés:International Journal of Molecular Sciences. - 22 : 3 (2021), p. 1-23. -
További szerzők:Holzknecht, Jeanett Galgóczy László (1950-) Tóth Liliána Poór Péter Ördög Attila Váradi Györgyi Kühbacher, Alexander Borics Attila Tóth Gábor K. Marx, Florentine Batta Gyula (1953-) (molekula-szerkezet kutató)
Pályázati támogatás:NKFIH FK 134343
Egyéb
NKFIH PD 134284
Egyéb
GINOP-2.3.2-15-2016-00008
GINOP
GINOP-2.3.3-15-2016-00004
GINOP
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2.

001-es BibID:BIBFORM127417
035-os BibID:(Scopus)85217647241 (WoS)001418685000001
Első szerző:Gai, Jiawei
Cím:Small disulfide proteins with antifungal impact: NMR experimental structures as compared to models of alphafold versions / Jiawei Gai, Márk File, Réka Erdei, András Czajlik, Florentine Marx, László Galgóczy, Györgyi Váradi, Gyula Batta
Dátum:2025
ISSN:1661-6596 1422-0067
Megjegyzések:In response to the growth of emerging resistance to conventional antifungal drugs, antifungal proteins (AFPs) of filamentous Ascomycetes origin have been discovered in recent years. Understanding the structure of AFPs is crucial for elucidating their antifungal mechanisms and developing new therapeutic agents. While nuclear magnetic resonance (NMR) has proven effective in determining the structures of small proteins, some AFP structures remain unresolved, necessitating the use of alternative prediction methods. Through bioinformatics analysis and heatmaps of amino acid sequence identity and similarity matrix, we categorized AFPs into three major classes and six subcategories, revealing structural and bioactivity differences. We employed AlphaFold (AF) to predict the 3D structures of six different AFPs, with predictions compared to NMR-derived structures. The results demonstrated a high degree of consistency between AF and NMR structures, with AF excelling in structural quality assessment and accurately capturing complex disulfide bond patterns. Both AF2 and AF3 models outperform the NMR model in overall structural quality and coherence, with AF3 showing the best performance. However, the limitations of AF should be considered, including its reduced accuracy in predicting multi-metal ion complexes, suboptimal performance in highly flexible or disordered regions, and its inability to account for multiple conformers, as it generates only a single dominant structure. Moreover, while AF3 accurately predicts all disulfide bond patterns, AF2 falls short in this regard. This study verifies the reliability of AF in the structural prediction of cysteine-rich AFPs while highlighting these constraints, offering important support for the rational design of new protein-based antifungal drugs.
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
antifungal proteins
AlphaFold
NMR
disulfide proteins
mini-protein
Megjelenés:International Journal of Molecular Sciences. - 26 : 3 (2025), p. 1-25. -
További szerzők:File Márk Erdei Réka Czajlik András (1975-) (gyógyszerész) Marx, Florentine Galgóczy László (1950-) Váradi Györgyi Batta Gyula (1953-) (molekula-szerkezet kutató)
Pályázati támogatás:NKFIH FK 134343
Egyéb
NKFIH K 146131
Egyéb
GINOP-2.3.2-15-2016-00008
GINOP
GINOP-2.3.3-15-2016-00004
GINOP
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3.

001-es BibID:BIBFORM077292
035-os BibID:(WoS)000466621200053 (Scopus)85061541042
Első szerző:Hajdu Dorottya (biológus)
Cím:Solution structure and novel insights into phylogeny and mode of action of the Neosartorya (Aspergillus) fischeri antifungal protein (NFAP) / Hajdu Dorottya, Huber Anna, Czajlik András, Tóth Liliána, Kele Zoltán, Kocsubé Sándor, Fizil Ádám, Marx Florentine, Galgóczy László, Batta Gyula
Dátum:2019
ISSN:0141-8130
Megjegyzések:Small, cysteine-rich and cationic antifungal proteins fromnatural 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.
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Neosartorya (Aspergillus) fischeri antifungal
protein (NFAP)
Nuclear magnetic resonance (NMR)
Antifungal mechanism
Megjelenés:International Journal of Biological Macromolecules. - 129 (2019), p. 511-522.
További szerzők:Huber Anna Czajlik András (1975-) (gyógyszerész) Tóth Liliána Kele Zoltán Kocsubé Sándor Fizil Ádám (1988-) (biológus) Marx, Florentine Galgóczy László (1950-) Batta Gyula (1953-) (molekula-szerkezet kutató)
Pályázati támogatás:GINOP-2.3.2-15-2016-00008
GINOP
GINOP-2.3.3-15-2016-00004
GINOP
PD 120808
OTKA
ANN 122833
OTKA
ANN 110821
OTKA
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4.

001-es BibID:BIBFORM086163
035-os BibID:(WoS)000537573200009 (Scopus)85081678362
Első szerző:Huber Anna
Cím:Two small, cysteine-rich and cationic antifungal proteins from Penicillium chrysogenum : a comparative study of PAF and PAFB / A. Huber, L. Galgóczy, G. Váradi, J. Holzknecht, A. Kakar, N. Malanovic, R. Leber, J. Koch, M. A. Keller, G. Batta, G. K. Tóth, F. Marx
Dátum:2020
ISSN:0005-2736
Megjegyzések:The filamentous fungus Penicillium chrysogenum Q176 secretes the antimicrobial proteins (AMPs) PAF and PAFB, which share a compact disulfide-bond mediated, beta-fold structure rendering them highly stable. These two AMPs effectively inhibit the growth of human pathogenic fungi in micromolar concentrations and exhibit antiviral potential without causing cytotoxic effects on mammalian cells in vitro and in vivo. The antifungal mechanism of action of both AMPs is closely linked to - but not solely dependent on - the lipid composition of the fungal cell membrane and requires a strictly regulated protein uptake into the cell, indicating that PAF and PAFB are not canonical membrane active proteins. Variations in their antifungal spectrum and their killing dynamics point towards a divergent mode of action related to their physicochemical properties and surface charge distribution. In this review, we relate characteristic features of PAF and PAFB to the current knowledge about other AMPs of different sources. In addition, we present original data that have never been published before to substantiate our assumptions and provide evidences that help to explain and understand better the mechanistic function of PAF and PAFB. Finally, we underline the promising potential of PAF and PAFB as future antifungal therapeutics.
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Antimicrobial proteins and peptides
Penicillium chrysogenum
beta-Fold structure
gamma-Core
Fungal membrane lipids
Endocytosis
Apoptosis
Megjelenés:Biochimica et Biophysica Acta (BBA). Biomembranes. - 1862 : 8 (2020), p. 1-14. -
További szerzők:Galgóczy László (1950-) Váradi Györgyi Holzknecht, Jeanett Kakar, A. Malanovic, N. Leber, R. Koch, J. Keller, M. A. Batta Gyula (1953-) (molekula-szerkezet kutató) Tóth Gábor K. Marx, Florentine
Pályázati támogatás:GINOP-2.3.2-15-2016-00008
GINOP
GINOP-2.3.3-15-2016-00004
GINOP
GINOP-2.3.2-15-2016-00014
GINOP
NKFI 20391-3/2018/FEKUSTRAT
Egyéb
TUDFO/47138-1/2019-ITM FIKP
Egyéb
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5.

001-es BibID:BIBFORM072198
035-os BibID:(WOS)000423429800003 (Scopus)85041371349
Első szerző:Huber Anna
Cím:New Antimicrobial Potential and Structural Properties of PAFB: A Cationic, Cysteine-Rich Protein from Penicillium chrysogenum Q176 / Anna Huber, Dorottya Hajdu, Doris Bratschun-Khan, Zoltán Gáspári, Mihayl Varbanov, Stéphanie Philippot, Ádám Fizil, András Czajlik, Zoltán Kele, Christoph Sonderegger, László Galgóczy, Andrea Bodor, Florentine Marx, Gyula Batta
Dátum:2018
ISSN:2045-2322
Megjegyzések:Small, cysteine-rich and cationic proteins with antimicrobial activity are produced by diverse organisms of all kingdoms and represent promising molecules for drug development. The ancestor of all industrial penicillin producing strains, the ascomycete Penicillium chryosgenum Q176, secretes the extensively studied antifungal protein PAF. However, the genome of this strain harbours at least two more genes that code for other small, cysteine-rich and cationic proteins with potential antifungal activity. In this study, we characterized the pafB gene product that shows high similarity to PgAFP from P. chrysogenum R42C. Although abundant and timely regulated pafB gene transcripts were detected, we could not identify PAFB in the culture broth of P. chrysogenum Q176. Therefore, we applied a P. chrysogenum-based expression system to produce sufficient amounts of recombinant PAFB to address unanswered questions concerning the structure and antimicrobial function. Nuclear magnetic resonance (NMR)-based analyses revealed a compact [beta]-folded structure, comprising five [beta]-strands connected by four solvent exposed and flexible loops and an "abcabc" disulphide bond pattern. We identified PAFB as an inhibitor of growth of human pathogenic moulds and yeasts. Furthermore, we document for the first time an anti-viral activity for two members of the small, cysteine-rich and cationic protein group from ascomycetes.
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Scientific Reports. - 8 : 1 (2018), p. 1751. -
További szerzők:Hajdu Dorottya (1987-) (biológus) Bratschun-Khan, Doris Gáspári Zoltán Varbanov, Mihayl Philippot, Stéphanie Fizil Ádám (1988-) (biológus) Czajlik András (1975-) (gyógyszerész) Kele Zoltán Sonderegger, Christoph Galgóczy László (1950-) Bodor Andrea Marx, Florentine Batta Gyula (1953-) (molekula-szerkezet kutató)
Pályázati támogatás:ANN 110821
OTKA
GINOP-2.3.2-15-2016-00008
GINOP
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6.

001-es BibID:BIBFORM123631
035-os BibID:(Scopus)85201638851 (WoS)001293298800001
Első szerző:Pavela Olivér
Cím:Mapping of the Lipid-Binding Regions of the Antifungal Protein NFAP2 by Exploiting Model Membranes / Olivér Pavela, Tünde Juhász, Liliána Tóth, András Czajlik, Gyula Batta, László Galgóczy, Tamás Beke-Somfai
Dátum:2024
ISSN:1549-9596
Megjegyzések:Fungal infections with high mortality rates represent an increasing health risk. The Neosartorya (Aspergillus) fischeri antifungal protein 2 (NFAP2) is a small, cysteine-rich, cationic protein exhibiting potent anti-Candida activity. As the underlying mechanism, pore formation has been demonstrated; however, molecular level details on its membrane disruption action are lacking. Herein, we addressed the lipid binding of NFAP2 using a combined computational and experimental approach to simple lipid compositions with various surface charge properties. Simulation results revealed binding preferences for negatively charged model membranes, where selectivity is mediated by anionic lipid components enriched at the protein binding site but also assisted by zwitterionic lipid species. Several potential binding routes initiated by various anchoring contacts were observed, which resulted in one main binding mode and a few variants, with NFAP2 residing on the membrane surface. Region (10)NCPNNCKHKKG(20) of the flexible N-terminal part of the protein showed potency to insert into the lipid bilayer, where the disulfide bond-stabilized short motif (CPNNC15)-C-11 could play a key role. In addition, several areas, including the beginning of the N-terminal (residues 1-8), played roles in facilitating initial membrane contacts. Besides, individual roles of residues such as Lys24, Lys32, Lys34, and Trp42 were also revealed by the simulations. Combined data demonstrated that the solution conformation was not perturbed markedly upon membrane interaction, and the folded part of the protein also contributed to stabilizing the bound state. Data also highlighted that the binding of NFAP2 to lipid vesicles is sensitively affected by environmental factors such as ionic strength. Electrostatic interactions driven by anionic lipids were found pivotal, explaining the reduced membrane activity observed under high salt conditions. Experimental data supported the lipid-selective binding mechanisms and pointed to salt-dependent effects, particularly to protein-assisted vesicle aggregation at low ionic strength. Our findings can contribute to the development of NFAP2-based anti-Candida agents and studies aiming at future medical use of peptide-based natural antifungal compounds.
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Journal of Chemical Information and Modeling. - 64 : 16 (2024), p. 6557-6569. -
További szerzők:Juhász Tünde Tóth Liliána Czajlik András (1975-) (gyógyszerész) Batta Gyula (1953-) (molekula-szerkezet kutató) Galgóczy László (1950-) Beke-Somfai Tamás
Pályázati támogatás:LP2016-2
MTA
NKFIH - NVKP_16-1-2016-0007
Egyéb
TKP2021-EGA-31
Egyéb
NKFIH - KKP22 144180
Egyéb
NKFIH - 2018-1.2.1-NKP-2018-00005
Egyéb
2020-1-1-2-PIACI-KFI_2020-00021
Egyéb
SA-87/2021
Egyéb
KEP-5/2021
Egyéb
FK134343
OTKA
K 146131
OTKA
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7.

001-es BibID:BIBFORM066900
035-os BibID:(WoS)000387640700002 (Scopus)84995519563
Első szerző:Sonderegger, Christoph
Cím:A Penicillium chrysogenum-based expression system for the production of small, cysteine-rich antifungal proteins for structural and functional analyses / Christoph Sonderegger, László Galgóczy, Sandra Garrigues, Ádám Fizil, Attila Borics, Paloma Manzanares, Nikoletta Hegedüs, Anna Huber, Jose F. Marcos, Gyula Batta, Florentine Marx
Dátum:2016
ISSN:1475-2859
Megjegyzések:Small, cysteine-rich and cationic antifungal proteins (APs) from filamentous ascomycetes, such as NFAP from Neosartorya fischeri and PAF from Penicillium chrysogenum, are promising candidates for novel drug development. A prerequisite for their application is a detailed knowledge about their structure-function relation and mode of action, which would allow protein modelling to enhance their toxicity and specificity. Technologies for structure analyses, such as electronic circular dichroism (ECD) or NMR spectroscopy, require highly purified samples and in case of NMR milligrams of uniformly 15N-/13C-isotope labelled protein. To meet these requirements, we developed a P. chrysogenum-based expression system that ensures sufficient amount and optimal purity of APs for structural and functional analyses.RESULTS:The APs PAF, PAF mutants and NFAP were expressed in a P. chrysogenum ?paf mutant strain that served as perfect microbial expression factory. This strain lacks the paf-gene coding for the endogenous antifungal PAF and is resistant towards several APs from other ascomycetes. The expression of the recombinant proteins was under the regulation of the strong paf promoter, and the presence of a paf-specific pre-pro sequence warranted the secretion of processed proteins into the supernatant. The use of defined minimal medium allowed a single-step purification of the recombinant proteins. The expression system could be extended to express PAF in the related fungus Penicillium digitatum, which does not produce detectable amounts of APs, demonstrating the versatility of the approach. The molecular masses, folded structures and antifungal activity of the recombinant proteins were analysed by ESI-MS, ECD and NMR spectroscopy and growth inhibition assays.CONCLUSION:This study demonstrates the implementation of a paf promoter driven expression cassettes for the production of cysteine-rich, cationic, APs in different Penicillium species. The system is a perfect tool for the generation of correctly folded proteins with high quality for structure-function analyses.KEYWORDS:Antifungal proteins; Electronic circular dichroism (ECD) spectroscopy; NFAP; Neosartorya fischeri; Nuclear magnetic resonance (NMR); PAF; Penicillium chrysogenum; Penicillium digitatum; Recombinant protein production
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Microbial Cell Factories. - 15 : 192 (2016), p. 1-14. -
További szerzők:Galgóczy László (1950-) Garrigues, Sandra Fizil Ádám (1988-) (biológus) Borics Attila Manzanares, Paloma Hegedűs Nikoletta Huber Anna Marcos, Jose F. Batta Gyula (1953-) (molekula-szerkezet kutató) Marx, Florentine
Pályázati támogatás:ANN110821
OTKA
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8.

001-es BibID:BIBFORM072756
035-os BibID:(WOS)000426785800002 (Scopus)85043257197
Első szerző:Tóth Liliána
Cím:Anti-Candidal Activity and Functional Mapping of Recombinant and Synthetic Neosartorya fischeri Antifungal Protein 2 (NFAP2) / Tóth Liliána, Váradi Györgyi, Borics Attila, Batta Gyula, Kele Zoltán, Vendrinszky Ákos, Tóth Roberta, Ficze Hargita, Tóth Gábor K., Vágvölgyi Csaba, Marx Florentine, Galgóczy László
Dátum:2018
ISSN:1664-302X
Megjegyzések:The increasing number of life-threatening Candida infections caused by antifungal drug-resistant strains urges the development of new therapeutic strategies. The small, cysteine-rich, and cationic Neosartorya fischeri antifungal protein 2 (NFAP2) effectively inhibits the growth of Candida spp. Limiting factors of its future application, are the low-yield production by the native producer, unavailable information about potential clinical application, and the unsolved relationship between the structure and function. In the present study we adopted a Penicillium chrysogenum-based expression system for bulk production of recombinant NFAP2. Furthermore, solid-phase peptide synthesis and native chemical ligation were applied to produce synthetic NFAP2. The average yield of recombinant and synthetic NFAP2 was 40- and 16-times higher than in the native producer, respectively. Both proteins were correctly processed, folded, and proved to be heat-stable. They showed the same minimal inhibitory concentrations as the native NFAP2 against clinically relevant Candida spp. Minimal inhibitory concentrations were higher in RPMI 1640 mimicking the human inner fluid than in a low ionic strength medium. The recombinant NFAP2 interacted synergistically with fluconazole, the first-line Candida therapeutic agent and significantly decreased its effective in vitro concentrations in RPMI 1640. Functional mapping with synthetic peptide fragments of NFAP2 revealed that not the evolutionary conserved antimicrobial ?-core motif, but the mid-N-terminal part of the protein influences the antifungal activity that does not depend on the primary structure of this region. Preliminary nucleic magnetic resonance measurements signed that the produced recombinant NFAP2 is suitable for further structural investigations.
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Neosartorya fischeri antifungal protein 2
recombinant protein
protein synthesis
anti-candidal activity
protein structure
functional mapping
Megjelenés:Frontiers in Microbiology. - 9 : 393 (2018), p. 1-12. -
További szerzők:Váradi Györgyi Borics Attila Batta Gyula (1953-) (molekula-szerkezet kutató) Kele Zoltán Vendrinszky Ákos Tóth Roberta Ficze Hargita Tóth Gábor K. Vágvölgyi Csaba Marx, Florentine Galgóczy László (1950-)
Pályázati támogatás:PD 120808, ANN 122833, ANN 110821
OTKA
GINOP-2.3.2-15-2016-00008
GINOP
GINOP-2.3.2-15-2016-00014
GINOP
GINOP-2.3.2-15-2016-00035
GINOP
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Intézményi repozitóriumban (DEA) tárolt változat
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9.

001-es BibID:BIBFORM042544
Első szerző:Váradi Györgyi
Cím:Synthesis of PAF, an antifungal protein from Penicillium chrysogenum by native chemical ligation / Györgyi Váradi, Gyula Batta, Zoltán Kele, László Galgóczi, Gábor K. Tóth
Dátum:2012
ISSN:1075-2617
Tárgyszavak:Természettudományok Kémiai tudományok poszter
Megjelenés:Journal of Peptide Science. - 18 : 1 (2012), p. S68. -
További szerzők:Batta Gyula (1953-) (molekula-szerkezet kutató) Kele Zoltán Galgóczy László (1950-) Tóth Gábor K.
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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10.

001-es BibID:BIBFORM113291
035-os BibID:(Scopus)85162082479 (WoS)001010056600001
Első szerző:Váradi Györgyi
Cím:Hard nut to crack: Solving the disulfide linkage pattern oftheNeosartorya(Aspergillus)fischeriantifungal protein 2 / Györgyi Váradi Zoltán Kele András Czajlik, Attila Borics, Gábor Bende, Csaba Papp, Gábor Rákhely,Gábor K. Tóth, Gyula Batta, László Galgóczy
Dátum:2023
ISSN:0961-8368
Megjegyzések:As a consequence of the fast resistance spreading, a limited number of drugs are available to treat fungal infections. Therefore, there is an urgent need to develop new antifungal treatment strategies. The features of a disulfide bond- stabilized antifungal protein, NFAP2 secreted by the mold Neosartorya (Asper- gillus) fischeri render it to be a promising template for future protein-based antifungal drug design, which requires knowledge about the native disulfide linkage pattern as it is one of the prerequisites for biological activity. However, in the lack of tryptic and chymotryptic proteolytic sites in the ACNCPNNCK sequence, the determination of the disulfide linkage pattern of NFAP2 is not easy with traditional mass spectrometry-based methods. According to in silico predictions working with a preliminary nuclear magnetic resonance (NMR) solution structure, two disulfide isomers of NFAP2 (abbacc and abbcac) were possible. Both were chemically synthesized; and comparative reversed-phase high-performance liquid chromatography, electronic circular dichroism and NMR spectroscopy analyses, and antifungal susceptibility and efficacy tests indicated that the abbcac is the native pattern. This knowledge allowed rational modification of NAFP2 to improve the antifungal efficacy and spectrum through the modulation of the evolutionarily conserved ?-core region, which is responsible for the activity of several antimicrobial peptides. Disruption of the steric structure of NFAP2 upon ?-core modification led to the conclusions that this motif may affect the formation of the biologically active three-dimensional structure, and that the ?-core modulation is not an efficient tool to improve the antifungal efficacy or to change the antifungal spectrum of NFAP2.
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Protein Science. - 32 : 7 (2023), p. 1-13. -
További szerzők:Kele Zoltán Czajlik András (1975-) (gyógyszerész) Borics Attila Bende Gábor Papp Csaba Rákhely Gábor Tóth Gábor K. Batta Gyula (1953-) (molekula-szerkezet kutató) Galgóczy László (1950-)
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Intézményi repozitóriumban (DEA) tárolt változat
Borító:

11.

001-es BibID:BIBFORM109184
035-os BibID:(Scopus)85149121543 (WoS)000939526000001
Első szerző:Váradi Györgyi
Cím:Confirmation of the Disulfide Connectivity and Strategies for Chemical Synthesis of the Four-Disulfide-Bond-Stabilized Aspergillus giganteus Antifungal Protein, AFP / Györgyi Váradi, Gyula Batta, László Galgóczy, Dorottya Hajdu, Ádám Fizil, András Czajlik, Máté Virágh, Zoltán Kele, Vera Meyer, Sascha Jung, Florentine Marx, Gábor K. Tóth
Dátum:2023
ISSN:0163-3864 1520-6025
Megjegyzések:Emerging fungal infections require new, more efficient antifungal agents and therapies. AFP, a protein from Aspergillus giganteus with four disulfide bonds, is a promising candidate because it selectively inhibits the growth of filamentous fungi. In this work, the reduced form of AFP was prepared using native chemical ligation. The native protein was synthesized via oxidative folding with uniform protection for cysteine thiols. AFP's biological activity depends heavily on the pattern of natural disulfide bonds. Enzymatic digestion and MS analysis provide proof for interlocking disulfide topology (abcdabcd) that was previously assumed. With this knowledge, a semi-orthogonal thiol protection method was designed. By following this strategy, out of a possible 105, only 6 disulfide isomers formed and 1 of them proved to be identical with the native protein. This approach allows the synthesis of analogs for examining structure-activity relationships and, thus, preparing AFP variants with higher antifungal activity.
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Journal of Natural Products. - 86 : 4 (2023), p. 782-790. -
További szerzők:Batta Gyula (1953-) (molekula-szerkezet kutató) Galgóczy László (1950-) Hajdu Dorottya (1987-) (biológus) Fizil Ádám (1988-) (biológus) Czajlik András (1975-) (gyógyszerész) Virágh Máté Kele Zoltán Meyer, Vera Jung, Sascha Marx, Florentine Tóth Gábor K.
Pályázati támogatás:NKFIH TKP2021-EGA-32
Egyéb
NKFIH FK 134343
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

12.

001-es BibID:BIBFORM056390
Első szerző:Váradi Györgyi
Cím:Synthesis of PAF, an Antifungal Protein from P. chrysogenum, by Native Chemical Ligation : Native Disulfide Pattern and Fold Obtained upon Oxidative Refolding / Györgyi Váradi, Gábor K. Tóth, Zoltán Kele, László Galgóczy, Ádám Fizil, Gyula Batta
Dátum:2013
ISSN:0947-6539
Megjegyzések:The folding of disulfide proteins is of considerable interest because knowledge of this may influence our present understanding of protein folding. However, sometimes even the disulfide pattern cannot be unequivocally determined by the available experimental techniques. For example, the structures of a few small antifungal proteins (PAF, AFP) have been disclosed recently using NMR spectroscopy but with some ambiguity in the actual disulfide pattern. For this reason, we carried out the chemical synthesis of PAF. Probing different approaches, the oxidative folding of the synthetic linear PAF yielded a folded protein that has identical structure and antifungal activity as the native PAF. In contrast, unfolded linear PAF was inactive, a result that may have implications concerning its redox state in the mode of action.
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
antifungal agents
NMR spectroscopy
peptides
protein folding
solid-phase synthesis
Molekulatudomány
Megjelenés:Chemistry-A European Journal 19 : 38 (2013), p. 12684-12692. -
További szerzők:Tóth Gábor K. Kele Zoltán Galgóczy László (1950-) Fizil Ádám (1988-) (biológus) Batta Gyula (1953-) (molekula-szerkezet kutató)
Pályázati támogatás:TÁMOP-4.2.1/B-09/1/KONV-2010-0005
TÁMOP
TÁMOP-4.2.1/B-09/1/KONV-2010-0007
TÁMOP
Szerkezeti biológia és molekuláris felismerés
TÁMOP-4.2.2.A-11/1/KONV-2012-0035
TÁMOP
CK 77515, K 105459, PD83355
OTKA
OMAA 83öu7 - Austrian-Hungarian Action
Egyéb
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Intézményi repozitóriumban (DEA) tárolt változat
Borító:
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