@article{MTMT:34084209,
	title = {Polymorphic amyloid nanostructures of hormone peptides involved in glucose homeostasis display reversible amyloid formation},
	url = {https://m2.mtmt.hu/api/publication/34084209},
	author = {Horváth, Dániel and Dürvanger, Zsolt and Karancsiné Menyhárd, Dóra and Sulyok-Eiler, Máté and Bencs, Fruzsina and Gyulai, Gergő and Horváth, Péter and Taricska, Nóra and Perczel, András},
	doi = {10.1038/s41467-023-40294-x},
	journal-iso = {NAT COMMUN},
	journal = {NATURE COMMUNICATIONS},
	volume = {14},
	unique-id = {34084209},
	issn = {2041-1723},
	abstract = {A large group of hormones are stored as amyloid fibrils in acidic secretion vesicles before they are released into the bloodstream and readopt their functional state. Here, we identify an evolutionarily conserved hexapeptide sequence as the major aggregation-prone region (APR) of gastrointestinal peptides of the glucagon family: xFxxWL. We determine nine polymorphic crystal structures of the APR segments of glucagon-like peptides 1 and 2, and exendin and its derivatives. We follow amyloid formation by CD, FTIR, ThT assays, and AFM. We propose that the pH-dependent changes of the protonation states of glutamate/aspartate residues of APRs initiate switching between the amyloid and the folded, monomeric forms of the hormones. We find that pH sensitivity diminishes in the absence of acidic gatekeepers and amyloid formation progresses over a broad pH range. Our results highlight the dual role of short aggregation core motifs in reversible amyloid formation and receptor binding.},
	year = {2023},
	eissn = {2041-1723},
	orcid-numbers = {Horváth, Dániel/0000-0001-8239-3933; Dürvanger, Zsolt/0000-0002-2652-4916; Karancsiné Menyhárd, Dóra/0000-0002-0095-5531; Sulyok-Eiler, Máté/0000-0002-3968-8776; Bencs, Fruzsina/0009-0003-9246-2228; Gyulai, Gergő/0000-0002-1352-2014; Horváth, Péter/0000-0001-7149-4173; Taricska, Nóra/0000-0002-9721-953X; Perczel, András/0000-0003-1252-6416}
}

@article{MTMT:34081394,
	title = {NMR-Chemical-Shift-Driven Protocol Reveals the Cofactor-Bound, Complete Structure of Dynamic Intermediates of the Catalytic Cycle of Oncogenic KRAS G12C Protein and the Significance of the Mg2+ Ion},
	url = {https://m2.mtmt.hu/api/publication/34081394},
	author = {Gadanecz, Márton and Fazekas, Zsolt and Pálfy, Gyula and Karancsiné Menyhárd, Dóra and Perczel, András},
	doi = {10.3390/ijms241512101},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {34081394},
	issn = {1661-6596},
	abstract = {In this work, catalytically significant states of the oncogenic G12C variant of KRAS, those of Mg2+-free and Mg2+-bound GDP-loaded forms, have been determined using CS-Rosetta software and NMR-data-driven molecular dynamics simulations. There are several Mg2+-bound G12C KRAS/GDP structures deposited in the Protein Data Bank (PDB), so this system was used as a reference, while the structure of the Mg2+-free but GDP-bound state of the RAS cycle has not been determined previously. Due to the high flexibility of the Switch-I and Switch-II regions, which also happen to be the catalytically most significant segments, only chemical shift information could be collected for the most important regions of both systems. CS-Rosetta was used to derive an “NMR ensemble” based on the measured chemical shifts, which, however, did not contain the nonprotein components of the complex. We developed a torsional restraint set for backbone torsions based on the CS-Rosetta ensembles for MD simulations, overriding the force-field-based parametrization in the presence of the reinserted cofactors. This protocol (csdMD) resulted in complete models for both systems that also retained the structural features and heterogeneity defined by the measured chemical shifts and allowed a detailed comparison of the Mg2+-bound and Mg2+-free states of G12C KRAS/GDP.},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Gadanecz, Márton/0009-0009-8076-7597; Fazekas, Zsolt/0000-0001-5007-4807; Pálfy, Gyula/0000-0003-1590-5331; Karancsiné Menyhárd, Dóra/0000-0002-0095-5531; Perczel, András/0000-0003-1252-6416}
}

@article{MTMT:34078730,
	title = {Inhibitor Design Strategy for Myostatin: Dynamics and Interaction Networks Define the Affinity and Release Mechanisms of the Inhibited Complexes},
	url = {https://m2.mtmt.hu/api/publication/34078730},
	author = {Nagy-Fazekas, Dóra and Fazekas, Zsolt and Taricska, Nóra and Stráner, Pál and Karancsiné Menyhárd, Dóra and Perczel, András},
	doi = {10.3390/molecules28155655},
	journal-iso = {MOLECULES},
	journal = {MOLECULES},
	volume = {28},
	unique-id = {34078730},
	issn = {1420-3049},
	abstract = {Myostatin, an important negative regulator of muscle mass, is a therapeutic target for muscle atrophic disorders such as muscular dystrophy. Thus, the inhibition of myostatin presents a strategy to treat these disorders. It has long been established that the myostatin prodomain is a strong inhibitor of the mature myostatin, and the minimum peptide of the prodomain—corresponding to the α1-helix of its lasso-region—responsible for the inhibitory efficiency was defined and characterized as well. Here we show that the minimum peptide segment based on the growth differentiation factor 11 (GDF11), which we found to be more helical in its stand-alone solvated stfate than the similar segment of myostatin, is a promising new base scaffold for inhibitor design. The proposed inhibitory peptides in their solvated state and in complex with the mature myostatin were analyzed by in silico molecule modeling supplemented with the electronic circular dichroism spectroscopy measurements. We defined the Gaussian–Mahalanobis mean score to measure the fraction of dihedral angle-pairs close to the desired helical region of the Ramachandran-plot, carried out RING analysis of the peptide-protein interaction networks and characterized the internal motions of the complexes using our rigid-body segmentation protocol. We identified a variant—11m2—that is sufficiently ordered both in solvent and within the inhibitory complex, forms a high number of contacts with the binding-pocket and induces such changes in its internal dynamics that lead to a rigidified, permanently locked conformation that traps this peptide in the binding site. We also showed that the naturally evolved α1-helix has been optimized to simultaneously fulfill two very different roles: to function as a strong binder as well as a good leaving group. It forms an outstanding number of non-covalent interactions with the mature core of myostatin and maintains the most ordered conformation within the complex, while it induces independent movement of the gate-keeper β-hairpin segment assisting the dissociation and also results in the least-ordered solvated form which provides extra stability for the dissociated state and discourages rebinding.},
	year = {2023},
	eissn = {1420-3049},
	orcid-numbers = {Taricska, Nóra/0000-0002-9721-953X; Stráner, Pál/0000-0003-2240-8501; Karancsiné Menyhárd, Dóra/0000-0002-0095-5531; Perczel, András/0000-0003-1252-6416}
}

@article{MTMT:34064337,
	title = {The regulation of the nephrin-nephrin distance by podocin mediates the interallelic interactions of the NPHS2 R229Q variant},
	url = {https://m2.mtmt.hu/api/publication/34064337},
	author = {Antal, Violetta and Schay, Gusztav and Kétszeri, Máté Csaba and Ungvari-Veres, Anita and Paszty, Katalin and Kellermayer, Miklos and Karancsiné Menyhárd, Dóra and Tory, Kálmán},
	journal-iso = {PEDIATR NEPHROL},
	journal = {PEDIATRIC NEPHROLOGY},
	volume = {38},
	unique-id = {34064337},
	issn = {0931-041X},
	year = {2023},
	eissn = {1432-198X},
	pages = {2262-2263},
	orcid-numbers = {Antal, Violetta/0000-0001-8658-6329; Kétszeri, Máté Csaba/0000-0001-7786-9837; Karancsiné Menyhárd, Dóra/0000-0002-0095-5531; Tory, Kálmán/0000-0002-0316-6212}
}

@article{MTMT:33307131,
	title = {A carbapenem antibiotic inhibiting a mammalian serine protease: structure of the acylaminoacyl peptidase–meropenem complex},
	url = {https://m2.mtmt.hu/api/publication/33307131},
	author = {Kiss-Szemán, Anna Júlia and Takács, Luca and Orgován, Zoltán and Stráner, Pál and Jákli, Imre and Schlosser, Gitta (Vácziné) and Masiulis, Simonas and Harmat, Veronika and Karancsiné Menyhárd, Dóra and Perczel, András},
	doi = {10.1039/D2SC05520A},
	journal-iso = {CHEM SCI},
	journal = {CHEMICAL SCIENCE},
	volume = {13},
	unique-id = {33307131},
	issn = {2041-6520},
	abstract = {The structure of porcine AAP (pAAP) in a covalently bound complex with meropenem was determined by cryo-EM to 2.1 Å resolution, showing the mammalian serine-protease inhibited by a carbapenem antibiotic.},
	year = {2022},
	eissn = {2041-6539},
	pages = {14264-14276},
	orcid-numbers = {Kiss-Szemán, Anna Júlia/0000-0002-3039-0324; Takács, Luca/0000-0002-4864-8872; Stráner, Pál/0000-0003-2240-8501; Schlosser, Gitta (Vácziné)/0000-0002-7637-7133; Harmat, Veronika/0000-0002-1866-9904; Karancsiné Menyhárd, Dóra/0000-0002-0095-5531; Perczel, András/0000-0003-1252-6416}
}

@CONFERENCE{MTMT:33138397,
	title = {Oly távol vagy tőlem, és mégis közel: patogén podocintársulások nefrin-nefrin távolságra gyakorolt hatása},
	url = {https://m2.mtmt.hu/api/publication/33138397},
	author = {Antal, Violetta and Schay, Gusztáv and Kétszeri, Máté Csaba and Ungvári-Veres, Anita and Pászty, Katalin and Kellermayer, Miklós and Karancsiné Menyhárd, Dóra and Tory, Kálmán},
	booktitle = {Magyar Gyermeknephrológiai Egyesület 2022. évi Kongresszusa},
	unique-id = {33138397},
	year = {2022},
	pages = {22-23},
	orcid-numbers = {Antal, Violetta/0000-0001-8658-6329; Kétszeri, Máté Csaba/0000-0001-7786-9837; Pászty, Katalin/0000-0003-2457-8555; Karancsiné Menyhárd, Dóra/0000-0002-0095-5531; Tory, Kálmán/0000-0002-0316-6212}
}

@article{MTMT:33040605,
	title = {Omicron Binding Mode: Contact Analysis and Dynamics of the Omicron Receptor-Binding Domain in Complex with ACE2},
	url = {https://m2.mtmt.hu/api/publication/33040605},
	author = {Fazekas, Zsolt and Karancsiné Menyhárd, Dóra and Perczel, András},
	doi = {10.1021/acs.jcim.2c00397},
	journal-iso = {J CHEM INF MODEL},
	journal = {JOURNAL OF CHEMICAL INFORMATION AND MODELING},
	volume = {62},
	unique-id = {33040605},
	issn = {1549-9596},
	abstract = {On 26 November 2021, the WHO classified the Omicron variant of the SARS-CoV-2 virus (B.1.1.529 lineage) as a Health, 2022). The Omicron variant contains as many as 26 unique mutations of effects not yet determined (Venkatakrishnan, A., Open Science Framework, 2021). Out of its total of 34 Spike protein mutations, 15 are located on the receptor-binding domain (Sthat directly contacts the angiotensin-converting enzyme 2 (ACE2) host receptor and is also a primary target for antibodies. Here, we studied the binding mode of the S-RBD domain of the Spike protein carrying the Omicron mutations and the globular domain of human ACE2 using molecular dynamics (MD) simulations. We identified new and key Omicron-specific interactions such as R-493 (of mutation Q493R), which forms salt bridges both with E(35 )and D(38 )of ACE2, Y-501 (N501Y), which forms an edge-to-face aromatic interaction with Y-41, and Y-505 (Y505H), which makes an H-bond with E-37 and K-353. The glycan chains of ACE2 also bind differently in the WT and Omicron variants in response to different charge distributions on the surface of Spike proteins. However, while the Omicron mutations considerably improve the overall electrostatic fit of the two interfaces, the total number of specific and favorable interactions between the two does not increase. The dynamics of the complexes are highly affected too, making the Omicron S-RBD:ACE2 complex more rigid; the two main interaction sites, Patches I and II, isolated in the WT complex, become connected in the Omicron complex through the alternating interaction of R-493 and R(498 )with E(35 )and D-38.},
	year = {2022},
	eissn = {1549-960X},
	pages = {3844-3853},
	orcid-numbers = {Karancsiné Menyhárd, Dóra/0000-0002-0095-5531; Perczel, András/0000-0003-1252-6416}
}

@article{MTMT:32924494,
	title = {The Importance of Mg2+‐free State in Nucleotide Exchange of Oncogenic K‐Ras Mutants},
	url = {https://m2.mtmt.hu/api/publication/32924494},
	author = {Pálfy, Gyula and Karancsiné Menyhárd, Dóra and Ákontz-Kiss, Hanna and Vida, István and Batta, Gyula and Tőke, Orsolya and Perczel, András},
	doi = {10.1002/chem.202201449},
	journal-iso = {CHEM-EUR J},
	journal = {CHEMISTRY-A EUROPEAN JOURNAL},
	volume = {28},
	unique-id = {32924494},
	issn = {0947-6539},
	abstract = {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.},
	keywords = {NMR spectroscopy; K-RAS; molecular dynamics; Slow dynamics; Ras cycle},
	year = {2022},
	eissn = {1521-3765},
	orcid-numbers = {Pálfy, Gyula/0000-0003-1590-5331; Karancsiné Menyhárd, Dóra/0000-0002-0095-5531; Batta, Gyula/0000-0002-0442-1828; Perczel, András/0000-0003-1252-6416}
}

@article{MTMT:32830377,
	title = {Cryo-EM structure of acylpeptide hydrolase reveals substrate selection by multimerization and a multi-state serine-protease triad},
	url = {https://m2.mtmt.hu/api/publication/32830377},
	author = {Kiss-Szemán, Anna Júlia and Stráner, Pál and Jákli, Imre and Hosogi, Naoki and Harmat, Veronika and Karancsiné Menyhárd, Dóra and Perczel, András},
	doi = {10.1039/D2SC02276A},
	journal-iso = {CHEM SCI},
	journal = {CHEMICAL SCIENCE},
	volume = {13},
	unique-id = {32830377},
	issn = {2041-6520},
	year = {2022},
	eissn = {2041-6539},
	pages = {7132-7142},
	orcid-numbers = {Kiss-Szemán, Anna Júlia/0000-0002-3039-0324; Stráner, Pál/0000-0003-2240-8501; Hosogi, Naoki/0000-0001-6662-1940; Harmat, Veronika/0000-0002-1866-9904; Karancsiné Menyhárd, Dóra/0000-0002-0095-5531; Perczel, András/0000-0003-1252-6416}
}

@article{MTMT:32817468,
	title = {High Salt Environment Disrupts the Regulatory Effect of Podocin on the Nephrin-Nephrin Distance},
	url = {https://m2.mtmt.hu/api/publication/32817468},
	author = {Antal, Violetta and Pap, Domonkos and Schay, Gusztáv and Kétszeri, Máté Csaba and Ungvári-Veres, Anita and Tulassay, Tivadar and Kellermayer, Miklós and Karancsiné Menyhárd, Dóra and Tory, Kálmán},
	doi = {10.1093/ndt/gfac097.002},
	journal-iso = {NEPHROL DIAL TRANSPL},
	journal = {NEPHROLOGY DIALYSIS TRANSPLANTATION},
	volume = {37},
	unique-id = {32817468},
	issn = {0931-0509},
	year = {2022},
	eissn = {1460-2385},
	pages = {i786-i788},
	orcid-numbers = {Antal, Violetta/0000-0001-8658-6329; Pap, Domonkos/0000-0002-1718-1210; Schay, Gusztáv/0000-0001-9512-3203; Kétszeri, Máté Csaba/0000-0001-7786-9837; Tulassay, Tivadar/0000-0002-5387-8103; Kellermayer, Miklós/0000-0002-5553-6553; Karancsiné Menyhárd, Dóra/0000-0002-0095-5531; Tory, Kálmán/0000-0002-0316-6212}
}