TY - JOUR AU - Tőke, Orsolya AU - Batta, Gyula TI - Dynamic Structures of Bioactive Proteins as Determined by Nuclear Magnetic Resonance JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 1 PG - 6 SN - 1661-6596 DO - 10.3390/ijms25010295 UR - https://m2.mtmt.hu/api/publication/34510717 ID - 34510717 AB - According to “Panta rhei”, a phrase by the ancient Greeks, you cannot enter the same river two times [...] LA - English DB - MTMT ER - TY - JOUR AU - Batta, Gyula TI - E. Kövér Katalin: 1956–2023 JF - MAGYAR KÉMIKUSOK LAPJA J2 - MAGY KEM LAP VL - 78 PY - 2023 IS - 6 SP - 191 EP - 191 PG - 1 SN - 0025-0163 UR - https://m2.mtmt.hu/api/publication/34076091 ID - 34076091 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Szilágyi, László AU - Batta, Gyula TI - In memoriam Kövér Katalin (1956-2023) JF - MAGYAR KÉMIAI FOLYÓIRAT - KÉMIAI KÖZLEMÉNYEK (1997-) J2 - MAGY KÉM FOLY KÉM KÖZL VL - 129 PY - 2023 IS - 1 SP - 4 EP - 6 PG - 3 SN - 1418-9933 DO - 10.24100/MKF.2023.01.04 UR - https://m2.mtmt.hu/api/publication/34065963 ID - 34065963 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Váradi, Györgyi AU - Kele, Zoltán AU - Czajlik, András AU - Borics, Attila AU - Bende, Gábor AU - Papp, Csaba Gergő AU - Rákhely, Gábor AU - Tóth, Gábor AU - Batta, Gyula AU - Galgóczi, László Norbert TI - Hard nut to crack: Solving the disulfide linkage pattern of the Neosartorya (Aspergillus) fischeri antifungal protein 2 JF - PROTEIN SCIENCE J2 - PROTEIN SCI VL - 32 PY - 2023 IS - 7 PG - 13 SN - 0961-8368 DO - 10.1002/pro.4692 UR - https://m2.mtmt.hu/api/publication/34043893 ID - 34043893 N1 - Department of Medical Chemistry, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, Debrecen, Hungary Department of Biochemistry, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary Laboratory of Chemical Biology, Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary Department of Biotechnology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Institute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary MTA-SZTE Biomimetic Systems Research Group, University of Szeged, Szeged, Hungary Fungal Genomics and Evolution Lab, Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network, Szeged, Hungary Export Date: 11 August 2023 CODEN: PRCIE Correspondence Address: Váradi, G.; Department of Medical Chemistry, Dóm tér 8, Hungary; email: varadi.gyorgyi@med.u-szeged.hu Correspondence Address: Galgóczy, L.; Department of Biotechnology, Közép fasor 52, Hungary; email: galgoczi@bio.u-szeged.hu Chemicals/CAS: disulfide, 16734-12-6; Antifungal Agents; Disulfides AB - 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 (Aspergillus) 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 gamma-core region, which is responsible for the activity of several antimicrobial peptides. Disruption of the steric structure of NFAP2 upon gamma-core modification led to the conclusions that this motif may affect the formation of the biologically active three-dimensional structure, and that the gamma-core modulation is not an efficient tool to improve the antifungal efficacy or to change the antifungal spectrum of NFAP2. LA - English DB - MTMT ER - TY - JOUR AU - Váradi, Györgyi AU - Batta, Gyula AU - Galgóczi, László Norbert AU - Hajdu, Dorottya Zsuzsanna AU - Fizil, Ádám AU - Czajlik, András AU - Virágh, Máté AU - Kele, Zoltán AU - Meyer, Vera AU - Jung, Sascha AU - Marx, Florentine AU - Tóth, Gábor TI - Confirmation of the Disulfide Connectivity and Strategies for Chemical Synthesis of the Four-Disulfide-Bond-Stabilized Aspergillus giganteus Antifungal Protein, AFP JF - JOURNAL OF NATURAL PRODUCTS J2 - J NAT PROD VL - 86 PY - 2023 IS - 4 SP - 782 EP - 790 PG - 9 SN - 0163-3864 DO - 10.1021/acs.jnatprod.2c00954 UR - https://m2.mtmt.hu/api/publication/33676645 ID - 33676645 N1 - Funding Agency and Grant Number: Hungarian National Research, Development [TKP2021-EGA-32]; Innovation Office-NKFIH; Hungarian National Research, Development and Innovation Office-NKFIH [FK 134343]; Austrian Science Fund [392923329]; Deutsche Forschungsgemeinschaft (DFG); [I1644-B20] Funding text: We thank D. Bratschun-Khan for her technical assistance. G.V. and G.K.T. were supported by the TKP2021-EGA-32 fund of the Hungarian National Research, Development, and Innovation Office-NKFIH, and L.G. was financed by the Hungarian National Research, Development and Innovation Office-NKFIH, FK 134343 project. This work was financed by the Austrian Science Fund (FWF I1644-B20) to F.M. and by the Deutsche Forschungsgemeinschaft (DFG, GRK2473 Bioactive Peptides project number 392923329) to S.J. and V.M. AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Czajlik, András AU - Batta, Ágnes AU - Kerner, Kinga AU - Fizil, Ádám AU - Hajdu, Dorottya Zsuzsanna AU - Hadháziné Raics, Mária AU - E Kövér, Katalin AU - Batta, Gyula TI - DMSO-Induced Unfolding of the Antifungal Disulfide Protein PAF and Its Inactive Variant: A Combined NMR and DSC Study JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 2 PG - 13 SN - 1661-6596 DO - 10.3390/ijms24021208 UR - https://m2.mtmt.hu/api/publication/33550734 ID - 33550734 N1 - Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, Debrecen, H-4032, Hungary Department of Biochemistry, Institute of Biochemistry and Molecular Biology, Semmelweis University, Tűzoltó utca 37-47, Budapest, H-1094, Hungary Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Egyetem tér 1, Debrecen, H-4032, Hungary Department of Inorganic and Analytical Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, Debrecen, H-4032, Hungary MTA-DE Molecular Recognition and Interaction Research Group, Department of Inorganic and Analytical Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, Debrecen, H-4032, Hungary Export Date: 18 September 2023 Correspondence Address: Batta, G.; Department of Organic Chemistry, Egyetem tér 1, Hungary; email: batta@unideb.hu AB - PAF and related antifungal proteins are promising antimicrobial agents. They have highly stable folds around room temperature due to the presence of 3–4 disulfide bonds. However, unfolded states persist and contribute to the thermal equilibrium in aqueous solution, and low-populated states might influence their biological impact. To explore such equilibria during dimethyl sulfoxide (DMSO)-induced chemical unfolding, we studied PAF and its inactive variant PAFD19S using nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). According to the NMR monitoring at 310 K, the folded structures disappear above 80 v/v% DMSO concentration, while the unfolding is completely reversible. Evaluation of a few resolved peaks from viscosity-compensated 15N-1H HSQC spectra of PAF yielded ∆G = 23 ± 7 kJ/M as the average value for NMR unfolding enthalpy. The NMR-based structures of PAF and the mutant in 50 v/v% DMSO/H2O mixtures were more similar in the mixed solvents then they were in water. The 15N NMR relaxation dynamics in the same mixtures verified the rigid backbones of the NMR-visible fractions of the proteins; still, enhanced dynamics around the termini and some loops were observed. DSC monitoring of the Tm melting point showed parabolic dependence on the DMSO molar fraction and suggested that PAF is more stable than the inactive PAFD19S. The DSC experiments were irreversible due to the applied broad temperature range, but still suggestive of the endothermic unfolding of PAF. LA - English DB - MTMT ER - TY - JOUR AU - Bakai-Bereczki, Ilona AU - Vimberg, Vladimir AU - Lőrincz, Eszter Boglárka AU - Papp, Henrietta AU - Nagy, Lajos AU - Kéki, Sándor AU - Batta, Gyula AU - Mitrović, Ana AU - Kos, Janko AU - Zsigmond, Áron AU - Hajdú, István AU - Lőrincz, Zsolt AU - Bajusz, Dávid AU - Petri, László AU - Hodek, Jan AU - Jakab, Ferenc AU - Keserű, György Miklós AU - Weber, Jan AU - Naesens, Lieve AU - Herczegh, Pál AU - Borbás, Anikó TI - Semisynthetic teicoplanin derivatives with dual antimicrobial activity against SARS-CoV-2 and multiresistant bacteria JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 12 PY - 2022 IS - 1 PG - 15 SN - 2045-2322 DO - 10.1038/s41598-022-20182-y UR - https://m2.mtmt.hu/api/publication/33119096 ID - 33119096 AB - Patients infected with SARS-CoV-2 risk co-infection with Gram-positive bacteria, which severely affects their prognosis. Antimicrobial drugs with dual antiviral and antibacterial activity would be very useful in this setting. Although glycopeptide antibiotics are well-known as strong antibacterial drugs, some of them are also active against RNA viruses like SARS-CoV-2. It has been shown that the antiviral and antibacterial efficacy can be enhanced by synthetic modifications. We here report the synthesis and biological evaluation of seven derivatives of teicoplanin bearing hydrophobic or superbasic side chain. All but one teicoplanin derivatives were effective in inhibiting SARS-CoV-2 replication in VeroE6 cells. One lipophilic and three perfluoroalkyl conjugates showed activity against SARS-CoV-2 in human Calu-3 cells and against HCoV-229E, an endemic human coronavirus, in HEL cells. Pseudovirus entry and enzyme inhibition assays established that the teicoplanin derivatives efficiently prevent the cathepsin-mediated endosomal entry of SARS-CoV-2, with some compounds inhibiting also the TMPRSS2-mediated surface entry route. The teicoplanin derivatives showed good to excellent activity against Gram-positive bacteria resistant to all approved glycopeptide antibiotics, due to their ability to dually bind to the bacterial membrane and cell-wall. To conclude, we identified three perfluoralkyl and one monoguanidine analog of teicoplanin as dual inhibitors of Gram-positive bacteria and SARS-CoV-2. LA - English DB - MTMT ER - TY - JOUR AU - Pálfy, Gyula AU - Karancsiné Menyhárd, Dóra AU - Ákontz-Kiss, Hanna AU - Vida, István AU - Batta, Gyula AU - Tőke, Orsolya AU - Perczel, András TI - The Importance of Mg2+‐free State in Nucleotide Exchange of Oncogenic K‐Ras Mutants JF - CHEMISTRY-A EUROPEAN JOURNAL J2 - CHEM-EUR J VL - 28 PY - 2022 IS - 59 PG - 14 SN - 0947-6539 DO - 10.1002/chem.202201449 UR - https://m2.mtmt.hu/api/publication/32924494 ID - 32924494 N1 - Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, 1/a Pázmány Péter stny., Budapest, 1117, Hungary MTA-ELTE Protein Modeling Research Group, Eötvös Loránd Research Network (ELKH), 1/a Pázmány Péter stny., Budapest, 1117, Hungary Hevesy György PhD School of Chemistry, Eötvös Loránd University, 1/a Pázmány Péter stny., Budapest, 1117, Hungary Structural Biology Research Group, Department of Organic Chemistry, University of Debrecen, 1 Egyetem tér, Debrecen, 4032, Hungary Laboratory for NMR Spectroscopy, Research Centre for Natural Sciences (RCNS), 2 Magyar tudósok körútja, Budapest, 1117, Hungary Cited By :3 Export Date: 6 April 2023 CODEN: CEUJE Correspondence Address: Perczel, A.; Laboratory of Structural Chemistry and Biology, 1/a Pázmány Péter stny., Hungary; email: perczel.andras@ttk.elte.hu AB - For efficient targeting of oncogenic K-Ras interaction sites, a mechanistic picture of the Ras-cycle is necessary. Herein, we used NMR relaxation techniques and molecular dynamics simulations to decipher the role of slow dynamics in wild-type and three oncogenic P-loop mutants of K-Ras. Our measurements reveal a dominant two-state conformational exchange on the ms timescale in both GDP- and GTP-bound KRas. The identified low-populated higher energy state in GDPloaded K-Ras has a conformation reminiscent of a nucleotidebound/Mg2+-free state characterized by shortened β2/β3-strands and a partially released switch-I region preparing K-Ras for the interaction with the incoming nucleotide exchange factor and subsequent reactivation. By providing insight into mutationspecific differences in K-Ras structural dynamics, our systematic analysis improves our understanding of prolonged K-Ras signaling and may aid the development of allosteric inhibitors targeting nucleotide exchange in K-Ras. LA - English DB - MTMT ER - TY - JOUR AU - Sánta, Anna AU - Czajlik, András AU - Batta, Gyula AU - Péterfia, Bálint AU - Gáspári, Zoltán TI - Resonance assignment of the Shank1 PDZ domain JF - BIOMOLECULAR NMR ASSIGNMENTS J2 - BIOMOL NMR ASSIGM VL - 16 PY - 2022 IS - 1 SP - 121 EP - 127 PG - 7 SN - 1874-2718 DO - 10.1007/s12104-022-10069-4 UR - https://m2.mtmt.hu/api/publication/32625251 ID - 32625251 N1 - Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Práter u. 50/A, Budapest, 1083, Hungary Faculty of Science and Technology, Institute of Chemistry, Department of Organic Chemistry, University of Debrecen, Egyetem tér 1, Debrecen, 4032, Hungary Export Date: 18 September 2023 Correspondence Address: Gáspári, Z.; Faculty of Information Technology and Bionics, Práter u. 50/A, Hungary; email: gaspari.zoltan@itk.ppke.hu AB - Shank proteins are among the most abundant and well-studied postsynaptic scaffold proteins. Their PDZ domain has unique characteristics as one of its loop regions flanking the ligand-binding site is uniquely long and has also been implicated in the formation of PDZ dimers. Here we report the initial characterization of the Shank1 PDZ domain by solution NMR spectroscopy. The assigned chemical shifts are largely consistent with the common features of PDZ domains in general and the available Shank PDZ crystal structures in particular. Our analysis suggests that under the conditions investigated, the domain is monomeric and the unique loop harbors a short helical segment, observed in only one of the known X-ray structures so far. Our work stresses the importance of solution-state investigations to fully decipher the functional relevance of the structural and dynamical features unique to Shank PDZ domains. LA - English DB - MTMT ER - TY - JOUR AU - Bakai-Bereczki, Ilona AU - Szűcs, Zsolt AU - Batta, Gyula AU - Nagy, Tamás Milán AU - Ostorházi, Eszter AU - E Kövér, Katalin AU - Borbás, Anikó AU - Herczegh, Pál TI - The First Dimeric Derivatives of the Glycopeptide Antibiotic Teicoplanin JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 15 PY - 2022 IS - 1 PG - 16 SN - 1424-8247 DO - 10.3390/ph15010077 UR - https://m2.mtmt.hu/api/publication/32584830 ID - 32584830 N1 - Megosztott első szerzőség. AB - Various dimeric derivatives of the glycopeptide antibiotic teicoplanin were prepared with the aim of increasing the activity of the parent compound against glycopeptide-resistant bacteria, primarily vancomycin-resistant enterococci. Starting from teicoplanin, four covalent dimers were prepared in two orientations, using an α,!-bis-isothiocyanate linker. Formation of a dimeric cobalt coordination complex of an N-terminal L-histidyl derivative of teicoplanin pseudoaglycone has been detected and its antibacterial activity evaluated. The Co(III)-induced dimerization of the histidyl derivative was demonstrated by DOSY experiments. Both the covalent and the complex dimeric derivatives showed high activity against VanA teicoplanin-resistant enterococci, but their activity against other tested bacterial strains did not exceed that of the monomeric compounds. LA - English DB - MTMT ER -