@article{MTMT:31677587,
	title = {Ligand-induced conformational rearrangements regulate the switch between membrane-proximal and distal functions of Rho kinase 2.},
	url = {https://m2.mtmt.hu/api/publication/31677587},
	author = {Hajdú, István and Szilágyi, András and Végh, Barbara and Wacha, András Ferenc and Györffy, Dániel and Gráczer, Éva Laura and Somogyi, Márk and Gál, Péter and Závodszky, Péter},
	doi = {10.1038/s42003-020-01450-x},
	journal-iso = {COMMUN BIOL},
	journal = {COMMUNICATIONS BIOLOGY},
	volume = {3},
	unique-id = {31677587},
	abstract = {Rho-associated protein kinase 2 (ROCK2) is a membrane-anchored, long, flexible, multidomain, multifunctional protein. Its functions can be divided into two categories: membrane-proximal and membrane-distal. A recent study concluded that membrane-distal functions require the fully extended conformation, and this conclusion was supported by electron microscopy. The present solution small-angle X-ray scattering (SAXS) study revealed that ROCK2 population is a dynamic mixture of folded and partially extended conformers. Binding of RhoA to the coiled-coil domain shifts the equilibrium towards the partially extended state. Enzyme activity measurements suggest that the binding of natural protein substrates to the kinase domain breaks up the interaction between the N-terminal kinase and C-terminal regulatory domains, but smaller substrate analogues do not. The present study reveals the dynamic behaviour of this long, dimeric molecule in solution, and our structural model provides a mechanistic explanation for a set of membrane-proximal functions while allowing for the existence of an extended conformation in the case of membrane-distal functions.},
	year = {2020},
	eissn = {2399-3642},
	orcid-numbers = {Szilágyi, András/0000-0002-1773-6861; Végh, Barbara/0000-0002-1405-4136; Wacha, András Ferenc/0000-0002-9609-0893}
}

@article{MTMT:31036023,
	title = {A versatile modular vector set for optimizing protein expression among bacterial, yeast, insect and mammalian hosts},
	url = {https://m2.mtmt.hu/api/publication/31036023},
	author = {Somogyi, Márk and Szimler, Tamás and Baksa, Attila and Végh, Barbara and Bakos, Tamás and Paréj, Katalin and Ádám, Csaba and Zsigmond, Áron and Megyeri, Márton and Flachner, Beáta and Sajó, Ráchel and Gráczer, Éva Laura and Závodszky, Péter and Hajdú, István and Beinrohr, László},
	doi = {10.1371/journal.pone.0227110},
	journal-iso = {PLOS ONE},
	journal = {PLOS ONE},
	volume = {14},
	unique-id = {31036023},
	issn = {1932-6203},
	year = {2019},
	eissn = {1932-6203},
	orcid-numbers = {Végh, Barbara/0000-0002-1405-4136; Bakos, Tamás/0000-0002-0569-8343; Beinrohr, László/0000-0001-6237-871X}
}

@article{MTMT:30625253,
	title = {New type of interaction between the SARAH domain of the tumour suppressor RASSF1A and its mitotic kinase Aurora A},
	url = {https://m2.mtmt.hu/api/publication/30625253},
	author = {Szimler, Tamás and Gráczer, Éva Laura and Györffy, Dániel and Végh, Barbara and Szilágyi, András and Hajdú, István and Závodszky, Péter and Kazinczyné Vas, Mária},
	doi = {10.1038/s41598-019-41972-x},
	journal-iso = {SCI REP},
	journal = {SCIENTIFIC REPORTS},
	volume = {9},
	unique-id = {30625253},
	issn = {2045-2322},
	year = {2019},
	eissn = {2045-2322},
	orcid-numbers = {Végh, Barbara/0000-0002-1405-4136; Szilágyi, András/0000-0002-1773-6861}
}

@article{MTMT:3023735,
	title = {Dual Role of the Active Site Residues of Thermus thermophilus 3-Isopropylmalate Dehydrogenase: Chemical Catalysis and Domain Closure.},
	url = {https://m2.mtmt.hu/api/publication/3023735},
	author = {Gráczer, Éva Laura and Szimler, Tamás and Garamszegi, A and Konarev, PV and Krezinger, Anikó and Oláh, Julianna and Pallo, A and Svergun, DI and Merli, A and Závodszky, Péter and Weiss, MS and Kazinczyné Vas, Mária},
	doi = {10.1021/acs.biochem.5b00839},
	journal-iso = {BIOCHEMISTRY-US},
	journal = {BIOCHEMISTRY},
	volume = {55},
	unique-id = {3023735},
	issn = {0006-2960},
	abstract = {The key active site residues K185, Y139, D217, D241, D245, and N102 of Thermus thermophilus 3-isopropylmalate dehydrogenase (Tt-IPMDH) have been replaced, one by one, with Ala. A drastic decrease in the kcat value (0.06% compared to that of the wild-type enzyme) has been observed for the K185A and D241A mutants. Similarly, the catalytic interactions (Km values) of these two mutants with the substrate IPM are weakened by more than 1 order of magnitude. The other mutants retained some (1-13%) of the catalytic activity of the wild-type enzyme and do not exhibit appreciable changes in the substrate Km values. The pH dependence of the wild-type enzyme activity (pK = 7.4) is shifted toward higher values for mutants K185A and D241A (pK values of 8.4 and 8.5, respectively). For the other mutants, smaller changes have been observed. Consequently, K185 and D241 may constitute a proton relay system that can assist in the abstraction of a proton from the OH group of IPM during catalysis. Molecular dynamics simulations provide strong support for the neutral character of K185 in the resting state of the enzyme, which implies that K185 abstracts the proton from the substrate and D241 assists the process via electrostatic interactions with K185. Quantum mechanics/molecular mechanics calculations revealed a significant increase in the activation energy of the hydride transfer of the redox step for both D217A and D241A mutants. Crystal structure analysis of the molecular contacts of the investigated residues in the enzyme-substrate complex revealed their additional importance (in particular that of K185, D217, and D241) in stabilizing the domain-closed active conformation. In accordance with this, small-angle X-ray scattering measurements indicated the complete absence of domain closure in the cases of D217A and D241A mutants, while only partial domain closure could be detected for the other mutants. This suggests that the same residues that are important for catalysis are also essential for inducing domain closure.},
	year = {2016},
	eissn = {1520-4995},
	pages = {560-574}
}

@article{MTMT:2807961,
	title = {Glutamate 270 plays an essential role in K+-activation and domain closure of Thermus thermophilus isopropylmalate dehydrogenase},
	url = {https://m2.mtmt.hu/api/publication/2807961},
	author = {Gráczer, Éva Laura and Palló, Anna and Oláh, Julianna and Szimler, Tamás and Konarev, Petr V and Svergun, Dmitri I and Merli, Angelo and Závodszky, Péter and Weiss, Manfred S and Kazinczyné Vas, Mária},
	doi = {10.1016/j.febslet.2014.12.005},
	journal-iso = {FEBS LETT},
	journal = {FEBS LETTERS},
	volume = {589},
	unique-id = {2807961},
	issn = {0014-5793},
	year = {2015},
	eissn = {1873-3468},
	pages = {240-245}
}

@article{MTMT:2785761,
	title = {Structural and energetic basis of isopropylmalate dehydrogenase enzyme catalysis},
	url = {https://m2.mtmt.hu/api/publication/2785761},
	author = {Palló, A and Oláh, Julianna and Gráczer, Éva Laura and Merli, A and Závodszky, Péter and Weiss, MS and Kazinczyné Vas, Mária},
	doi = {10.1111/febs.13044},
	journal-iso = {FEBS J},
	journal = {FEBS JOURNAL},
	volume = {281},
	unique-id = {2785761},
	issn = {1742-464X},
	abstract = {The three-dimensional structure of the enzyme 3-isopropylmalate dehydrogenase from the bacterium Thermus thermophilus in complex with Mn2+, its substrate isopropylmalate and its co-factor product NADH at 2.0 Å resolution features a fully closed conformation of the enzyme. Upon closure of the two domains, the substrate and the co-factor are brought into precise relative orientation and close proximity, with a distance between the C2 atom of the substrate and the C4N atom of the pyridine ring of the co-factor of approximately 3.0 Å. The structure further shows binding of a K+ ion close to the active site, and provides an explanation for its known activating effect. Hence, this structure is an excellent mimic for the enzymatically competent complex. Using high-level QM/MM calculations, it may be demonstrated that, in the observed arrangement of the reactants, transfer of a hydride from the C2 atom of 3-isopropylmalate to the C4N atom of the pyridine ring of NAD+ is easily possible, with an activation energy of approximately 15 kcal·mol-1. The activation energy increases by approximately 4-6 kcal·mol-1 when the K+ ion is omitted from the calculations. In the most plausible scenario, prior to hydride transfer the ε-amino group of Lys185 acts as a general base in the reaction, aiding the deprotonation reaction of 3-isopropylmalate prior to hydride transfer by employing a low-barrier proton shuttle mechanism involving a water molecule.},
	keywords = {ARTICLE; CATALYSIS; PYRIDINE; nonhuman; Manganese; calculation; X-RAY CRYSTALLOGRAPHY; carboxy terminal sequence; enzyme structure; reduced nicotinamide adenine dinucleotide; potassium ion; enzyme conformation; enzyme active site; enzyme binding; Thermus thermophilus; 3 isopropylmalate dehydrogenase; ISOPROPYLMALATE DEHYDROGENASE; Oxidative decarboxylation; QM/MM calculations; general base catalysis},
	year = {2014},
	eissn = {1742-4658},
	pages = {5063-5076}
}

@article{MTMT:2604041,
	title = {Drugs Against Mycobacterium Tuberculosis 3-Isopropylmalate Dehydrogenase Can be Developed using Homologous Enzymes as Surrogate Targets},
	url = {https://m2.mtmt.hu/api/publication/2604041},
	author = {Gráczer, Éva Laura and Bacsó, András and Kónya, Dénes and Kazi, A and Soós, Tibor and Molnár, Laura and Szimler, Tamás and Beinrohr, László and Szilágyi, András and Závodszky, Péter and Kazinczyné Vas, Mária},
	journal-iso = {PROTEIN PEPTIDE LETT},
	journal = {PROTEIN AND PEPTIDE LETTERS},
	volume = {21},
	unique-id = {2604041},
	issn = {0929-8665},
	abstract = {3-Isopropylmalate dehydrogenase (IPMDH) from Mycobacterium tuberculosis (Mtb) may be a target for specific drugs against this pathogenic bacterium. We have expressed and purified Mtb IPMDH and determined its physical-chemical and enzymological properties. Size-exclusion chromatography and dynamic light scattering measurements (DLS) suggest a tetrameric structure for Mtb IPMDH, in contrast to the dimeric structure of most IPMDHs. The kinetic properties (kcat and Km values) of Mtb IPMDH and the pH-dependence of kcat are very similar to both Escherichia coli (Ec) and Thermus thermophilus (Tt) IPMDHs. The stability of Mtb IPMDH in 8 M urea is close to that of the mesophilic counterpart, Ec IPMDH, both of them being much less stable than the thermophilic (Tt) enzyme. Two known IPMDH inhibitors, O-methyl oxalohydroxamate and 3-methylmercaptomalate, have been synthesised. Their inhibitory effects were found to be independent of the origin of IPMDHs. Thus, experiments with either Ec or Tt IPMDH would be equally relevant for designing specific inhibitory drugs against Mtb IPMDH.},
	year = {2014},
	eissn = {1875-5305},
	pages = {1295-1307},
	orcid-numbers = {Beinrohr, László/0000-0001-6237-871X; Szilágyi, András/0000-0002-1773-6861}
}

@article{MTMT:3027798,
	title = {Transient kinetics show isomerisation steps in the kinetic pathway of Isopropylmalate Dehydrogenase},
	url = {https://m2.mtmt.hu/api/publication/3027798},
	author = {Gráczer, Éva Laura and Lionne, C and Zavodszky, P and Chaloin, L and Vas, M},
	journal-iso = {EUR BIOPHYS J},
	journal = {EUROPEAN BIOPHYSICS JOURNAL},
	volume = {42},
	unique-id = {3027798},
	issn = {0175-7571},
	year = {2013},
	eissn = {1432-1017},
	pages = {S176-S176}
}

@article{MTMT:2339846,
	title = {Transient kinetic studies reveal isomerization steps along the kinetic pathway of Thermusthermophilus 3-isopropylmalate dehydrogenase},
	url = {https://m2.mtmt.hu/api/publication/2339846},
	author = {Gráczer, Éva Laura and Lionne, Corinne and Závodszky, Péter and Chaloin, Laurent and Kazinczyné Vas, Mária},
	doi = {10.1111/febs.12191},
	journal-iso = {FEBS J},
	journal = {FEBS JOURNAL},
	volume = {280},
	unique-id = {2339846},
	issn = {1742-464X},
	year = {2013},
	eissn = {1742-4658},
	pages = {1764-1772}
}

@article{MTMT:2226151,
	title = {Selectivity of kinases on the activation of tenofovir, an anti-HIV agent},
	url = {https://m2.mtmt.hu/api/publication/2226151},
	author = {Matkovicsné Varga, Andrea and Gráczer, Éva Laura and Chaloin, L and Liliom, Károly and Závodszky, Péter and Lionne, C and Kazinczyné Vas, Mária},
	doi = {10.1016/j.ejps.2012.11.007},
	journal-iso = {EUR J PHARM SCI},
	journal = {EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES},
	volume = {48},
	unique-id = {2226151},
	issn = {0928-0987},
	abstract = {Nucleoside analogues, used in HIV-therapy, need to be 
		phosphorylated by cellular enzymes in order to become potential 
		substrates for HIV reverse transcriptase. After incorporation 
		into the viral DNA chain, because of lacking of their 3'-
		hydroxyl groups, they stop the elongation process and lead to 
		the death of the virus. Phosphorylation of the HIV-drug 
		derivative, tenofovir monophosphate was tested with the 
		recombinant mammalian nucleoside diphosphate kinase (NDPK), 3-
		phosphoglycerate kinase (PGK), creatine kinase (CK) and pyruvate 
		kinase (PK). Among them, only CK was found to phosphorylate 
		tenofovir monophosphate with a reasonable rate (about 45-fold 
		lower than with its natural substrate, ADP), while PK exhibits 
		even lower, but still detectable activity (about 1000-fold lower 
		compared to the value with ADP). On the other hand, neither NDPK 
		nor PGK has any detectable activity on tenofovir monophosphate. 
		The absence of activity with PGK is surprising, since the drug 
		tenofovir competitively inhibits both CK and PGK towards their 
		nucleotide substrates, with similar inhibitory constants, KI of 
		2.9 and 4.8 mM, respectively. Computer modelling (docking) of 
		tenofovir mono- or diphosphate forms to these four kinases 
		suggests that the requirement of large-scale domain closure for 
		functioning (as for PGK) may largely restrict their 
		applicability for phosphorylation/activation of pro-drugs having 
		a structure similar to tenofovir monophosphate. © 2012 Elsevier 
		B.V. All rights reserved.},
	keywords = {ARTICLE; human; priority journal; enzyme activation; unclassified drug; virus DNA; phosphoglycerate kinase; creatine kinase; enzyme phosphorylation; rna directed dna polymerase; drug selectivity; computer model; tenofovir; drug metabolite; recombinant enzyme; Molecular docking; enzyme active site; drug activation; pyruvate kinase; nucleoside diphosphate kinase; tenofovir monophosphate; 3-Phospho-D-glycerate kinase},
	year = {2013},
	eissn = {1879-0720},
	pages = {307-315},
	orcid-numbers = {Matkovicsné Varga, Andrea/0000-0001-9165-5368; Liliom, Károly/0000-0002-7177-6872}
}