TY - JOUR AU - Kovács, Hilda AU - Jakusch, Tamás AU - May, Nóra Veronika AU - Tóth, Szilárd AU - Szakács, Gergely AU - Enyedy, Éva Anna TI - Complex formation of ML324, the histone demethylase inhibitor, with essential metal ions: Relationship between solution chemistry and anticancer activity JF - JOURNAL OF INORGANIC BIOCHEMISTRY J2 - J INORG BIOCHEM VL - 255 PY - 2024 PG - 12 SN - 0162-0134 DO - 10.1016/j.jinorgbio.2024.112540 UR - https://m2.mtmt.hu/api/publication/34761990 ID - 34761990 LA - English DB - MTMT ER - TY - JOUR AU - Jambrich, M.A. AU - Tusnády, Gábor AU - Dobson, László TI - How AlphaFold2 shaped the structural coverage of the human transmembrane proteome JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 13 PY - 2023 IS - 1 PG - 11 SN - 2045-2322 DO - 10.1038/s41598-023-47204-7 UR - https://m2.mtmt.hu/api/publication/34401705 ID - 34401705 AB - AlphaFold2 (AF2) provides a 3D structure for every known or predicted protein, opening up new prospects for virtually every field in structural biology. However, working with transmembrane protein molecules pose a notorious challenge for scientists, resulting in a limited number of experimentally determined structures. Consequently, algorithms trained on this finite training set also face difficulties. To address this issue, we recently launched the TmAlphaFold database, where predicted AlphaFold2 structures are embedded into the membrane plane and a quality assessment (plausibility of the membrane-embedded structure) is provided for each prediction using geometrical evaluation. In this paper, we analyze how AF2 has improved the structural coverage of membrane proteins compared to earlier years when only experimental structures were available, and high-throughput structure prediction was greatly limited. We also evaluate how AF2 can be used to search for (distant) homologs in highly diverse protein families. By combining quality assessment and homology search, we can pinpoint protein families where AF2 accuracy is still limited, and experimental structure determination would be desirable. © 2023, The Author(s). LA - English DB - MTMT ER - TY - JOUR AU - Tusnády, Gábor AU - Zeke, András AU - Kálmán, Zsófia Etelka AU - Fatoux, Marie AU - Ricard-Blum, Sylvie AU - Gibson, Toby J AU - Dobson, László TI - LeishMANIAdb: a comparative resource for Leishmania proteins JF - DATABASE-JOURNAL OF BIOLOGICAL DATABASES AND CURATION J2 - DATABASE-OXFORD VL - 2023 PY - 2023 PG - 10 SN - 1758-0463 DO - 10.1093/database/baad074 UR - https://m2.mtmt.hu/api/publication/34279727 ID - 34279727 N1 - Protein Bioinformatics Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Magyar Tudósok körútja 2, Budapest, 1117, Hungary Department of Bioinformatics, Semmelweis University, Tu˝zoltó u. 7, Budapest, 1094, Hungary Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Práter u. 50/A, Budapest, 1083, Hungary ICBMS UMR CNRS 5246, University Lyon, 1, Rue Victor Grignard, Villeurbanne, 69622, France UMR CNRS 5086, University Lyon 1, 7 Passage du Vercors, Lyon, 69367, France Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, Heidelberg, 69117, Germany Cited By :2 Export Date: 21 March 2024 Correspondence Address: Dobson, L.; Protein Bioinformatics Research Group, Magyar Tudósok körútja 2, Hungary; email: dobon.laszlo@ttk.hu AB - Leishmaniasis is a detrimental disease causing serious changes in quality of life and some forms can lead to death. The disease is spread by the parasite Leishmania transmitted by sandfly vectors and their primary hosts are vertebrates including humans. The pathogen penetrates host cells and secretes proteins (the secretome) to repurpose cells for pathogen growth and to alter cell signaling via host–pathogen protein–protein interactions). Here, we present LeishMANIAdb, a database specifically designed to investigate how Leishmania virulence factors may interfere with host proteins. Since the secretomes of different Leishmania species are only partially characterized, we collated various experimental evidence and used computational predictions to identify Leishmania secreted proteins to generate a user-friendly unified web resource allowing users to access all information available on experimental and predicted secretomes. In addition, we manually annotated host–pathogen interactions of 211 proteins and the localization/function of 3764 transmembrane (TM) proteins of different Leishmania species. We also enriched all proteins with automatic structural and functional predictions that can provide new insights in the molecular mechanisms of infection. Our database may provide novel insights into Leishmania host–pathogen interactions and help to identify new therapeutic targets for this neglected disease. LA - English DB - MTMT ER - TY - JOUR AU - Németh, Krisztina AU - László, Zsófia AU - Biró, Adrienn AU - Szatmári, Ágnes AU - Cserép, Balázs Gergely AU - Várady, György AU - Bakos, Éva AU - Laczka, Csilla AU - Kele, Péter TI - Organic anion transporting polypeptide 3A1 (OATP3A1)-gated bioorthogonal labeling of intracellular proteins JF - MOLECULES J2 - MOLECULES VL - 28 PY - 2023 IS - 6 PG - 10 SN - 1420-3049 DO - 10.3390/molecules28062521 UR - https://m2.mtmt.hu/api/publication/33688209 ID - 33688209 N1 - Chemical Biology Research Group, Institute of Organic Chemistry, RCNS, Magyar Tudósok Krt. 2, Budapest, H-1117, Hungary Molecular Cell Biology Research Group, Institute of Enzymology, RCNS, Magyar Tudósok Krt. 2, Budapest, H-1117, Hungary Membrane Protein Research Group, Institute of Enzymology, RCNS, Magyar Tudósok Krt. 2, Budapest, H-1117, Hungary Export Date: 19 April 2023 CODEN: MOLEF Correspondence Address: Németh, K.; Chemical Biology Research Group, Magyar Tudósok Krt. 2, Hungary; email: nemeth.krisztina@ttk.hu Correspondence Address: Kele, P.; Chemical Biology Research Group, Magyar Tudósok Krt. 2, Hungary; email: kele.peter@ttk.hu Chemicals/CAS: protein, 67254-75-5; Fluorescent Dyes; Organic Anion Transporters; Proteins Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, NKFIH-K-138518, NKFIH-K-143581, VEKOP-2.3.3-15-2016-00011 Funding text 1: Present work was supported by the National Research, Development and Innovation Office of Hungary (NKFIH-K-143581, NKFIH-K-138518 and VEKOP-2.3.3-15-2016-00011). AB - Organic anion transporting polypeptides (OATPs) were found to readily deliver membrane impermeable, tetrazine bearing fluorescent probes into cells. This feature was explored in OATP3A1 conditioned bio-orthogonal labeling schemes of various intracellular proteins in live cells. Confocal microscopy and super-resolution microscopy (STED) studies have shown that highly specific and efficient staining of the selected intracellular proteins can be achieved with the otherwise non-permeable probes when OATP3A1 is present in the cell membrane of cells. Such a transport protein linked bio-orthogonal labeling scheme is believed to be useful in OATP3A1 activity-controlled protein expression studies in the future. © 2023 by the authors. LA - English DB - MTMT ER - TY - JOUR AU - Langó, Tamás AU - Kuffa, Katalin Rita AU - Tóth, Gábor AU - Turiák, Lilla AU - Drahos, László AU - Tusnády, Gábor TI - Comprehensive Discovery of the Accessible Primary Amino Group-Containing Segments from Cell Surface Proteins by Fine-Tuning a High-Throughput Biotinylation Method JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 1 PG - 17 SN - 1661-6596 DO - 10.3390/ijms24010273 UR - https://m2.mtmt.hu/api/publication/33586305 ID - 33586305 AB - Cell surface proteins, including transmembrane and other surface-anchored proteins, play a key role in several critical cellular processes and have a strong diagnostic value. The development of quick and robust experimental methods remains vital for the accurate and comprehensive characterization of the cell surface subproteome of individual cells. Here we present a high-throughput technique which relies on the biotinylation of the accessible primary amino groups in the extracellular segments of the proteins, using HL60 as a model cell line. Several steps of the method have been thoroughly optimized to capture labeled surface proteins selectively and in larger quantities. These include the following: improving the efficiency of the cell surface biotinylation; reducing the endogen protease activity; applying an optimal amount of affinity column and elution steps for labeled peptide enrichment; and examining the effect of various solid-phase extraction methods, different HPLC gradients, and various tandem mass spectrometry settings. Using the optimized workflow, we identified at least 1700 surface-associated individual labeled peptides (~6000–7000 redundant peptides) from the model cell surface in a single nanoHPLC-MS/MS run. The presented method can provide a comprehensive and specific list of the cell surface available protein segments that could be potential targets in various bioinformatics and molecular biology research. © 2022 by the authors. LA - English DB - MTMT ER - TY - JOUR AU - Pivarcsik, Tamás AU - Pósa, Vivien AU - Kovács, Hilda AU - May, Nóra Veronika AU - Spengler, Gabriella AU - Pósa, Szonja P. AU - Tóth, Szilárd AU - Nezafat Yazdi, Zeinab AU - Laczka, Csilla AU - Ugrai, Imre AU - Szatmári, István AU - Szakács, Gergely AU - Enyedy, Éva Anna TI - Metal Complexes of a 5-Nitro-8-Hydroxyquinoline-Proline Hybrid with Enhanced Water Solubility Targeting Multidrug Resistant Cancer Cells JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 1 PG - 27 SN - 1661-6596 DO - 10.3390/ijms24010593 UR - https://m2.mtmt.hu/api/publication/33532438 ID - 33532438 N1 - MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7, Szeged, H-6720, Hungary Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Dóm tér 7, Szeged, H-6720, Hungary Centre for Structural Science, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok krt. 2, Budapest, H-1117, Hungary Department of Medical Microbiology, Albert Szent-Györgyi Health Center, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, Szeged, H-6725, Hungary Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok krt. 2, Budapest, H-1117, Hungary National Laboratory for Drug Research and Development, Magyar Tudósok krt. 2, Budapest, H-1117, Hungary Institute of Pharmaceutical Chemistry and Stereochemistry Research Group, Eötvös Loránd Research Network, University of Szeged, Eötvös u. 6, Szeged, H-6720, Hungary Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria Cited By :2 Export Date: 20 September 2023 Correspondence Address: Enyedy, É.A.; MTA-SZTE Lendület Functional Metal Complexes Research Group, Dóm tér 7, Hungary; email: enyedy@chem.u-szeged.hu Chemicals/CAS: ferric ion, 20074-52-6; ferrous ion, 15438-31-0; nitroxoline, 4008-48-4; zinc ion, 23713-49-7; proline, 147-85-3, 7005-20-1; ruthenium, 7440-18-8; water, 7732-18-5; Antineoplastic Agents; Coordination Complexes; Ferric Compounds; Ferrous Compounds; Ions; Ligands; nitroxoline; Organometallic Compounds; Proline; Ruthenium; Water Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, FK128751, K138518, LP2019-6/2019, RRF-2.3.1-21-2022-00015, TKP-2021-EGA-32 Funding text 1: This work was supported by National Research, Development and Innovation Fund (Hungary) through projects TKP-2021-EGA-32, FK128751, RRF-2.3.1-21-2022-00015 and K138518. The support of the “Lendület” Programme (ELKH, LP2019-6/2019) is also acknowledged (É.A.E.). AB - Multidrug resistance (MDR) in cancer is one of the major obstacles of chemotherapy. We have recently identified a series of 8-hydroxyquinoline Mannich base derivatives with MDR-selective toxicity, however with limited solubility. In this work, a novel 5-nitro-8-hydroxyquinoline-proline hybrid and its Rh(η5-C5Me5) and Ru(η6-p-cymene) complexes with excellent aqueous solubility were developed, characterized, and tested against sensitive and MDR cells. Complex formation of the ligand with essential metal ions was also investigated using UV-visible, circular dichroism, 1H NMR (Zn(II)), and electron paramagnetic resonance (Cu(II)) spectroscopic methods. Formation of mono and bis complexes was found in all cases with versatile coordination modes, while tris complexes were also formed with Fe(II) and Fe(III) ions, revealing the metal binding affinity of the ligand at pH 7.4: Cu(II) > Zn(II) > Fe(II) > Fe(III). The ligand and its Rh(III) complex displayed enhanced cytotoxicity against the resistant MES-SA/Dx5 and Colo320 human cancer cell lines compared to their chemosensitive counterparts. Both organometallic complexes possess high stability in solution, however the Ru(II) complex has lower chloride ion affinity and slower ligand exchange processes, along with the readiness to lose the arene ring that is likely connected to its inactivity. LA - English DB - MTMT ER - TY - JOUR AU - Kaci, Hana AU - Bodnárová, Slávka AU - Fliszár-Nyúl, Eszter AU - Lemli, Beáta AU - Pelantová, Helena AU - Valentová, Kateřina AU - Bakos, Éva AU - Laczka, Csilla AU - Poór, Miklós TI - Interaction of luteolin, naringenin, and their sulfate and glucuronide conjugates with human serum albumin, cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) enzymes and organic anion transporting polypeptide (OATP1B1 and OATP2B1) transporters JF - BIOMEDICINE & PHARMACOTHERAPY J2 - BIOMED PHARMACOTHER VL - 157 PY - 2023 PG - 12 SN - 0753-3322 DO - 10.1016/j.biopha.2022.114078 UR - https://m2.mtmt.hu/api/publication/33294693 ID - 33294693 N1 - Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar tudósok krt. 2, Budapest, H-1117, Hungary Doctoral School of Biology, Institute of Biology, Eötvös Loránd University, Pázmány P. stny. 1/C, Budapest, H-1117, Hungary Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, Pécs, H-7624, Hungary Food Biotechnology Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs, H-7624, Hungary Green Chemistry Research Group, János Szentágothai Research Center, University of Pécs, Ifjúság útja 20, Pécs, H-7624, Hungary Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, Prague, CZ-142, Czech Republic Cited By :1 Export Date: 4 September 2023 CODEN: BIPHE Correspondence Address: Poór, M.; Department of Pharmacology, Rókus u. 2, Hungary; email: poor.miklos@pte.hu AB - Luteolin and naringenin are flavonoids found in various foods/beverages and present in certain dietary supplements. After a high intake of these flavonoids, their sulfate and glucuronide conjugates reach micromolar concentrations in the bloodstream. Some pharmacokinetic interactions of luteolin and naringenin have been investigated in previous studies; however, only limited data are available in regard to their metabolites. In this study, we aimed to investigate the interactions of the sulfate and glucuronic acid conjugates of luteolin and naringenin with human serum albumin, cytochrome P450 (CYP2C9, 2C19, and 3A4) enzymes, and organic anion transporting polypeptide (OATP1B1 and OATP2B1) transporters. Our main findings are as follows: (1) Sulfate conjugates formed more stable complexes with albumin than the parent flavonoids. (2) Luteolin and naringenin conjugates showed no or only weak inhibitory action on the CYP enzymes examined. (3) Certain conjugates of luteolin and naringenin are potent inhibitors of OATP1B1 and/or OATP2B1 enzymes. (4) Conjugated metabolites of luteolin and naringenin may play an important role in the pharmacokinetic interactions of these flavonoids. LA - English DB - MTMT ER - TY - JOUR AU - Dobson, László AU - Szekeres, Levente István AU - Gerdán, Csongor AU - Langó, Tamás AU - Zeke, András AU - Tusnády, Gábor TI - TmAlphaFold database: membrane localization and evaluation of AlphaFold2 predicted alpha-helical transmembrane protein structures JF - NUCLEIC ACIDS RESEARCH J2 - NUCLEIC ACIDS RES VL - 51 PY - 2023 IS - D1 SP - D517 EP - D522 PG - 6 SN - 0305-1048 DO - 10.1093/nar/gkac928 UR - https://m2.mtmt.hu/api/publication/33213881 ID - 33213881 N1 - Protein Bioinformatics Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Magyar Tudósok körútja 2, Budapest, H-1117, Hungary Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, Heidelberg, 69117, Germany Cited By :18 Export Date: 2 April 2024 CODEN: NARHA Correspondence Address: Tusnády, G.E.; Protein Bioinformatics Research Group, Magyar Tudósok körútja 2, Hungary; email: tusnady.gabor@ttk.hu AB - AI-driven protein structure prediction, most notably AlphaFold2 (AF2) opens new frontiers for almost all fields of structural biology. As traditional structure prediction methods for transmembrane proteins were both complicated and error prone, AF2 is a great help to the community. Complementing the relatively meager number of experimental structures, AF2 provides 3D predictions for thousands of new alpha-helical membrane proteins. However, the lack of reliable structural templates and the fact that AF2 was not trained to handle phase boundaries also necessitates a delicate assessment of structural correctness. In our new database, Transmembrane AlphaFold database (TmAlphaFold database), we apply TMDET, a simple geometry-based method to visualize the likeliest position of the membrane plane. In addition, we calculate several parameters to evaluate the location of the protein into the membrane. This also allows TmAlphaFold database to show whether the predicted 3D structure is realistic or not. The TmAlphaFold database is available at https://tmalphafold.ttk.hu/. LA - English DB - MTMT ER - TY - JOUR AU - Zeke, András AU - Takács, Tamás AU - Sok, Péter Dániel AU - Németh, Krisztina AU - Kirsch, Klára AU - Egri, Péter AU - Póti, Ádám Levente AU - Bento, Isabel AU - Tusnády, Gábor AU - Reményi, Attila TI - Structural insights into the pSer/pThr dependent regulation of the SHP2 tyrosine phosphatase in insulin and CD28 signaling JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 13 PY - 2022 IS - 1 PG - 14 SN - 2041-1723 DO - 10.1038/s41467-022-32918-5 UR - https://m2.mtmt.hu/api/publication/33121755 ID - 33121755 AB - Serine/threonine phosphorylation of insulin receptor substrate (IRS) proteins is well known to modulate insulin signaling. However, the molecular details of this process have mostly been elusive. While exploring the role of phosphoserines, we have detected a direct link between Tyr-flanking Ser/Thr phosphorylation sites and regulation of specific phosphotyrosine phosphatases. Here we present a concise structural study on how the activity of SHP2 phosphatase is controlled by an asymmetric, dual phosphorylation of its substrates. The structure of SHP2 has been determined with three different substrate peptides, unveiling the versatile and highly dynamic nature of substrate recruitment. What is more, the relatively stable pre-catalytic state of SHP2 could potentially be useful for inhibitor design. Our findings not only show an unusual dependence of SHP2 catalytic activity on Ser/Thr phosphorylation sites in IRS1 and CD28, but also suggest a negative regulatory mechanism that may also apply to other tyrosine kinase pathways as well. LA - English DB - MTMT ER - TY - JOUR AU - Jójárt, Rebeka AU - Laczkó-Rigó, Réka AU - Klement, Máté AU - Kőhl, Gabriella AU - Kecskeméti, Gábor AU - Laczka, Csilla AU - Mernyák, Erzsébet TI - Design, synthesis and biological evaluation of novel estrone phosphonates as high affinity organic anion-transporting polypeptide 2B1 (OATP2B1) inhibitors JF - BIOORGANIC CHEMISTRY J2 - BIOORG CHEM VL - 112 PY - 2021 PG - 12 SN - 0045-2068 DO - 10.1016/j.bioorg.2021.104914 UR - https://m2.mtmt.hu/api/publication/32009571 ID - 32009571 N1 - Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Drug Resistance Research Group instead of Membrane Protein Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Magyar tudósok körútja 2Budapest H-1117, Hungary Department of Medicinal Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Export Date: 26 August 2021 LA - English DB - MTMT ER -