TY - JOUR AU - Tóth, Balázs István AU - Bahar, Bazeli AU - Annelies, Janssens AU - Lisztes, Erika AU - Racskó, Márk AU - Kelemen, Balázs AU - Herczeg, Mihály AU - Nagy, Tamás Milán AU - E Kövér, Katalin AU - Argha, Mitra AU - Attila, Borics AU - Bíró, Tamás AU - Thomas, Voets TI - Direct modulation of TRPM8 ion channels by rapamycin and analog macrolide immunosuppressants JF - ELIFE J2 - ELIFE PY - 2024 SN - 2050-084X UR - https://m2.mtmt.hu/api/publication/34722559 ID - 34722559 N1 - preprint DOI-ja: 10.1101/2024.02.01.578392 LA - English DB - MTMT ER - TY - JOUR AU - Gönczi, Mónika AU - Teixeira, João M. C. AU - Barrera-Vilarmau, Susana AU - Mediani, Laura AU - Antoniani, Francesco AU - Nagy, Tamás Milán AU - Fehér, Krisztina AU - Ráduly, Zsolt AU - Ambrus, Viktor Attila AU - Tőzsér, József AU - Barta, Endre AU - E Kövér, Katalin AU - Csernoch, László AU - Carra, Serena AU - Fuxreiter, Mónika TI - Alternatively spliced exon regulates context-dependent MEF2D higher-order assembly during myogenesis JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 14 PY - 2023 PG - 13 SN - 2041-1723 DO - 10.1038/s41467-023-37017-7 UR - https://m2.mtmt.hu/api/publication/33693788 ID - 33693788 AB - During muscle cell differentiation, the alternatively spliced, acidic β-domain potentiates transcription of Myocyte-specific Enhancer Factor 2 (Mef2D). Sequence analysis by the FuzDrop method indicates that the β-domain can serve as an interaction element for Mef2D higher-order assembly. In accord, we observed Mef2D mobile nuclear condensates in C2C12 cells, similar to those formed through liquid-liquid phase separation. In addition, we found Mef2D solid-like aggregates in the cytosol, the presence of which correlated with higher transcriptional activity. In parallel, we observed a progress in the early phase of myotube development, and higher MyoD and desmin expression. In accord with our predictions, the formation of aggregates was promoted by rigid β-domain variants, as well as by a disordered β-domain variant, capable of switching between liquid-like and solid-like higher-order states. Along these lines, NMR and molecular dynamics simulations corroborated that the β-domain can sample both ordered and disordered interactions leading to compact and extended conformations. These results suggest that β-domain fine-tunes Mef2D higher-order assembly to the cellular context, which provides a platform for myogenic regulatory factors and the transcriptional apparatus during the developmental process. LA - English DB - MTMT ER - TY - THES AU - Nagy, Tamás Milán TI - Understanding structure and dynamics with advanced NMR and in silico methods PY - 2022 DO - 10.13140/RG.2.2.18393.80482 UR - https://m2.mtmt.hu/api/publication/33209861 ID - 33209861 AB - One of the most powerful tools for studying proteins at molecular level is Nuclear Magnetic Resonance (NMR) spectroscopy. Throughout my undergraduate years, the first encounters with this technique were structural studies carried out on cyclopeptides probing the microenvironment of disulfide bonds. In parallel, I was introduced to intrinsically disordered proteins (IDP) in the form of mini proteins modeling the β-domain of the MEF2D transcription factor. With the hope for establishing a relationship between protein dynamics and function, these studies evolved over the PhD years to better understand the unexpected behavior of the MEF2D protein mutants. NMR relaxation, diffusion measurements, and chemical shift-based calculations were complemented by computational studies (molecular dynamics (MD) simulations). Nanoscale Differential Scanning Fluorometry (NanoDSF) measurements of our collaborators confirmed the oligomerization of one of the peptides, which process might be also essential to understand the biological function of these complex molecules. I have also participated in the development of NMR methods resulting in reduced measurement times and high-quality spectral data with enriched information. To this end, different experiments were combined in NOAH-type single and double BANGO NMR sequences. In addition, exceptionally rapid measurements without relaxation delays were achieved in the NO Relaxation Delay (NORD) spectroscopy. In minutes, complete correlation maps were obtained for small and medium-sized molecules, allowing their quick and unambiguous resonance assignment. LA - English DB - MTMT ER - TY - JOUR AU - Angeli, Cserne AU - Nagy, Tamás Milán AU - Horváth, Levente AU - Varga, Mónika AU - Szekeres, András AU - Tóth, Gábor AU - Janáky, Tamás AU - Szolomájer, János AU - Kovács, Melinda AU - E Kövér, Katalin AU - Bartók, Tibor TI - Preparation of 3- O -, 5- O - and N -palmitoyl derivatives of fumonisin B 1 toxin and their characterisation with NMR and LC-HRMS methods JF - FOOD ADDITIVES AND CONTAMINANTS PART A - CHEMISTRY ANALYSIS CONTROL EXPOSURE AND RISK ASSESSMENT J2 - FOOD ADDIT CONTAM A VL - 39 PY - 2022 IS - 10 SP - 1759 EP - 1771 PG - 13 SN - 1944-0049 DO - 10.1080/19440049.2022.2116112 UR - https://m2.mtmt.hu/api/publication/33085154 ID - 33085154 AB - We have previously published six esterified O-acyl (EFB1) and three N-acyl fumonisin B-1 derivatives extracted from rice cultures inoculated with Fusarium verticillioides, amongst these the identification of N-palmitoyl-FB1 has been clearly established in a spiking experiment. At that time, it was assumed that as in the case of O-acyl-FB1 derivatives, linoleic-, oleic- or palmitic acid esterify through the OH group on the 3C or 5C atom of the carbon chain of the fumonisins. In our most recent experiments, we have synthetically acylated the FB1 toxin and subsequently purified 3-O-palmitoyl- and 5-O-palmitoyl-FB1 toxins in addition to the N-palmitoyl-FB1 toxin. They were identified and characterised using H-1 and C-13 NMR as well as LC-HRMS. Our aim was the identification of the previously detected O-acyl-FB1 derivatives over the course of a spiking experiment, which were obtained through the solid-phase fermentation of Fusarium verticillioides. By spiking the three synthesized and identified components one-by-one into the fungal culture extract and analysing these cultures using LC-MS, it was clearly demonstrated that the F. verticillioides strain produced both the 5-O-palmitoyl-FB1 and N-palmitoyl-FB1 toxins, but did not produce 3-O-palmitoyl-FB1. Thus, it is highly probable that the components thought to be 3-O-acyl-(linoleoyl-, oleoyl-, palmitoyl-) FB1 derivatives in our previous communication are presumably 10-O-acyl-FB1 derivatives. Since these acylated FB1 derivatives can occur naturally in e.g. maize, the use of these synthesized components as reference materials is of great importance in order to obtain accurate qualitative and quantitative data on the occurrence of acylated fumonisins in different matrices including maize based feed samples. The production of these substances has also made it possible to test their toxicity in cell culture and small animal experiments. LA - English DB - MTMT ER - TY - JOUR AU - Timári, István AU - Nagy, Tamás Milán AU - E Kövér, Katalin AU - Sørensen, Ole W. TI - Synergy and sensitivity-balance in concatenating experiments in NO Relaxation Delay NMR (NORD) JF - CHEMICAL COMMUNICATIONS J2 - CHEM COMMUN VL - 58 PY - 2022 IS - 15 SP - 2516 EP - 2519 PG - 4 SN - 1359-7345 DO - 10.1039/D1CC06663C UR - https://m2.mtmt.hu/api/publication/32607584 ID - 32607584 AB - The NMR experiment design strategy of NO Relaxation Delay (NORD), introduced mostly as an idealized theoretical approach, is extended and put to practical use by considering synergy and sensitivity-balance in concatenation of experiments. It is illustrated by a novel experiment, NORD {HMBC}–{HSQC}–{TOCSY}, where magnetization of non-13C attached protons effectively is channeled from the TOCSY spectrum toward primarily the least sensitive spectrum of HMBC. The experiment is expected to find its place as a full-package NMR method for metabolomics, carbohydrates, peptides and small-molecules in general. 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 - TY - JOUR AU - Nagy, Tamás Milán AU - E Kövér, Katalin AU - Sørensen, Ole W. TI - NORD: NO Relaxation Delay NMR spectroscopy JF - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION J2 - ANGEW CHEM INT EDIT VL - 60 PY - 2021 IS - 24 SP - 13587 EP - 13590 PG - 4 SN - 1433-7851 DO - 10.1002/anie.202102487 UR - https://m2.mtmt.hu/api/publication/31938298 ID - 31938298 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary [NKFI/OTKA NN 128368]; European Regional Development FundEuropean Commission [GINOP-2.3.3-15-2016-00004, GINOP-2.3.2-15-2016-00044] Funding text: This research was supported by the National Research, Development and Innovation Office of Hungary (grant NKFI/OTKA NN 128368) and co-financed by the European Regional Development Fund (projects GINOP-2.3.3-15-2016-00004 and GINOP-2.3.2-15-2016-00044). AB - The novel concept of NORD (NO relaxation delay) NMR spectroscopy is introduced. The idea is to design concatenated experiments in a way that the magnetization used in the first relaxes toward equilibrium during the second and vice versa, thus saving instrument time. Applications include complete well-resolved 1H-1H and 1H-13C one-bond and long-range correlation maps of an 80 mM solution of a trisaccharide recorded in less than two minutes and hydrocortisone with extensive spectral overlap. LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Tamás Milán AU - E Kövér, Katalin AU - Sørensen, Ole W. TI - Double and adiabatic BANGO for concatenating two NMR experiments relying on the same pool of magnetization JF - JOURNAL OF MAGNETIC RESONANCE J2 - J MAGN RESON VL - 316 PY - 2020 PG - 4 SN - 1090-7807 DO - 10.1016/j.jmr.2020.106767 UR - https://m2.mtmt.hu/api/publication/31334838 ID - 31334838 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary [NKFI/OTKA NN 128368]; European Regional Development FundEuropean Union (EU) [GINOP-2.3.3-15-2016-00004, GINOP-2.3.2-15-2016-00044, GINOP-2.3.2-15-2016-00008] Funding text: This research was supported by the National Research, Development and Innovation Office of Hungary (grant NKFI/OTKA NN 128368) and co-financed by the European Regional Development Fund (projects GINOP-2.3.3-15-2016-00004, GINOP-2.3.2-15-2016-00044 and GINOP-2.3.2-15-2016-00008). AB - It is shown how the same pool of magnetization can be tapped twice in two different concatenations ofthree experiments into a single pulse sequence with only one relaxation delay. This is accomplished byusing the BANGO pulse sequence element twice for independent rotations of1H magnetization attachedor not attached to13C and it includes a refinement of BANGO with an adiabatic13C inversion pulse result-ing in improved tolerance to a spread in1JCHcoupling constants that translates directly into improvedsensitivity of the modular experiment relying on1H magnetization attached to13C. The two new pulsesequences are SEA XLOC–HMBC–H2OBC/2BOB and SEA XLOC(ZQ)–SEA XLOC(2Q)–H2OBC/2BOB whichboth represent a rapid route to complete heteronuclear one-bond and long-rangeJCHcorrelation mapsfor small molecules, as is demonstrated on ibuprofen and prednisolone. LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Tamás Milán AU - Gyöngyösi, Tamás AU - E Kövér, Katalin AU - Sorensen, Ole W. TI - BANGO SEA XLOC/HMBC-H2OBC: complete heteronuclear correlation within minutes from one NMR pulse sequence JF - CHEMICAL COMMUNICATIONS J2 - CHEM COMMUN VL - 55 PY - 2019 IS - 81 SP - 12208 EP - 12211 PG - 4 SN - 1359-7345 DO - 10.1039/c9cc06253j UR - https://m2.mtmt.hu/api/publication/30931203 ID - 30931203 AB - Novel NMR experiments, BANGO SEA XLOC-H2OBC or BANGO HMBC-H2OBC, can deliver complete heteronuclear correlation maps on a time scale of minutes for small molecules. By way of example, it is demonstrated that all intra- and inter-residue H-1 and C-13 correlations and assignments of a trisaccharide are obtained in 20 or 5 minutes of instrument time without or with 25% NUS, respectively. LA - English DB - MTMT ER - TY - CONF AU - Nagy, Tamás Milán AU - Gyöngyösi, Tamás AU - Boros, Sándor AU - Burkhard, Luy AU - Kövér, Katalin ED - Jeffrey, C Hoch TI - Boosting the NMR assignment of small to medium-sized molecules with different edited variants of HSQC-CLIP-COSY experiment T2 - ABSTRACT BOOK PY - 2018 PG - 1 DO - 10.13140/RG.2.2.19714.12489 UR - https://m2.mtmt.hu/api/publication/3417841 ID - 3417841 LA - English DB - MTMT ER -