@article{MTMT:35134753,
	title = {Mitochondrial Alpha-Keto Acid Dehydrogenase Complexes: Recent Developments on Structure and Function in Health and Disease},
	url = {https://m2.mtmt.hu/api/publication/35134753},
	author = {Szabó, Eszter and Nagy, Bálint and Czajlik, András and Komlódi, Tímea and Ozohanics, Olivér and Tretter, László and Ambrus, Attila},
	doi = {10.1007/978-3-031-58843-3_13},
	journal-iso = {SUB-CELL BIOCHEM},
	journal = {SUB-CELLULAR BIOCHEMISTRY},
	volume = {104},
	unique-id = {35134753},
	issn = {0306-0225},
	year = {2024},
	eissn = {2542-8810},
	pages = {295-381},
	orcid-numbers = {Szabó, Eszter/0000-0002-9634-2771; Nagy, Bálint/0000-0003-3669-7041; Komlódi, Tímea/0000-0001-9876-1411; Ozohanics, Olivér/0000-0002-2705-9921; Tretter, László/0000-0001-5638-2886; Ambrus, Attila/0000-0001-6014-3175}
}

@article{MTMT:33686272,
	title = {Lipoamide dehydrogenase (LADH) deficiency: medical perspectives of the structural and functional characterization of LADH and its pathogenic variants},
	url = {https://m2.mtmt.hu/api/publication/33686272},
	author = {Szabó, Eszter and Ambrus, Attila},
	doi = {10.1007/s42977-023-00155-6},
	journal-iso = {BIOL FUTURA},
	journal = {BIOLOGIA FUTURA},
	volume = {74},
	unique-id = {33686272},
	issn = {2676-8615},
	year = {2023},
	eissn = {2676-8607},
	pages = {109-118},
	orcid-numbers = {Szabó, Eszter/0000-0002-9634-2771; Ambrus, Attila/0000-0001-6014-3175}
}

@article{MTMT:33749248,
	title = {A mitokondriális α-ketosav-dehidrogenáz enzimkomplexek működése, szerkezete és szabályozása},
	url = {https://m2.mtmt.hu/api/publication/33749248},
	author = {Wittinger, Soma and Szabó, Eszter and Ambrus, Attila},
	journal-iso = {BIOKÉMIA},
	journal = {BIOKÉMIA: A MAGYAR BIOKÉMIAI EGYESÜLET FOLYÓIRATA},
	volume = {47},
	unique-id = {33749248},
	issn = {0133-8455},
	year = {2023},
	eissn = {2060-8152},
	pages = {19-31},
	orcid-numbers = {Szabó, Eszter/0000-0002-9634-2771; Ambrus, Attila/0000-0001-6014-3175}
}

@article{MTMT:34075046,
	title = {Structural and Biochemical Investigation of Selected Pathogenic Mutants of the Human Dihydrolipoamide Dehydrogenase},
	url = {https://m2.mtmt.hu/api/publication/34075046},
	author = {Szabó, Eszter and Nemes-Nikodém, Éva and Vass, Krisztina Rubina and Zámbó, Zsófia Melinda and Zrupko, E. and Törőcsik, Beáta and Ozohanics, Olivér and Nagy, Bálint and Ambrus, Attila},
	doi = {10.3390/ijms241310826},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {34075046},
	issn = {1661-6596},
	abstract = {Clinically relevant disease-causing variants of the human dihydrolipoamide dehydrogenase (hLADH, hE3), a common component of the mitochondrial α-keto acid dehydrogenase complexes, were characterized using a multipronged approach to unravel the molecular pathomechanisms that underlie hLADH deficiency. The G101del and M326V substitutions both reduced the protein stability and triggered the disassembly of the functional/obligate hLADH homodimer and significant FAD losses, which altogether eventually manifested in a virtually undetectable catalytic activity in both cases. The I12T-hLADH variant proved also to be quite unstable, but managed to retain the dimeric enzyme form; the LADH activity, both in the forward and reverse catalytic directions and the affinity for the prosthetic group FAD were both significantly compromised. None of the above three variants lent themselves to an in-depth structural analysis via X-ray crystallography due to inherent protein instability. Crystal structures at 2.89 and 2.44 Å resolutions were determined for the I318T- and I358T-hLADH variants, respectively; structure analysis revealed minor conformational perturbations, which correlated well with the residual LADH activities, in both cases. For the dimer interface variants G426E-, I445M-, and R447G-hLADH, enzyme activities and FAD loss were determined and compared against the previously published structural data. © 2023 by the authors.},
	keywords = {Reactive oxygen species; X-RAY CRYSTALLOGRAPHY; Lipoamide Dehydrogenase; disease-causing mutation; alpha-keto acid dehydrogenase complexes},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Szabó, Eszter/0000-0002-9634-2771; Vass, Krisztina Rubina/0000-0002-1584-7154; Zámbó, Zsófia Melinda/0000-0001-8657-8556; Törőcsik, Beáta/0000-0002-9838-3710; Ozohanics, Olivér/0000-0002-2705-9921; Nagy, Bálint/0000-0003-3669-7041; Ambrus, Attila/0000-0001-6014-3175}
}

@article{MTMT:32707799,
	title = {Current Approaches in Molecular Enzymology},
	url = {https://m2.mtmt.hu/api/publication/32707799},
	author = {Szabó, Eszter and Ambrus, Attila},
	doi = {10.3390/life12030336},
	journal-iso = {LIFE-BASEL},
	journal = {LIFE-BASEL},
	volume = {12},
	unique-id = {32707799},
	abstract = {Enzymes are the main executioners of living organisms [...]},
	year = {2022},
	eissn = {2075-1729},
	orcid-numbers = {Szabó, Eszter/0000-0002-9634-2771; Ambrus, Attila/0000-0001-6014-3175}
}

@article{MTMT:31917407,
	title = {Structure of the dihydrolipoamide succinyltransferase (E2) component of the human alpha-ketoglutarate dehydrogenase complex (hKGDHc) revealed by cryo-EM and cross-linking mass spectrometry. Implications for the overall hKGDHc structure.},
	url = {https://m2.mtmt.hu/api/publication/31917407},
	author = {Nagy, Bálint and Polak, Martin and Ozohanics, Olivér and Zámbó, Zsófia Melinda and Szabó, Eszter and Hubert, Ágnes and Jordan, Frank and Novaček, Jiří and Ádám, Veronika and Ambrus, Attila},
	doi = {10.1016/j.bbagen.2021.129889},
	journal-iso = {BBA-GEN SUBJECTS},
	journal = {BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS},
	volume = {1865},
	unique-id = {31917407},
	issn = {0304-4165},
	abstract = {The human mitochondrial alpha-ketoglutarate dehydrogenase complex (hKGDHc) converts KG to succinyl-CoA and NADH. Malfunction of and reactive oxygen species generation by the hKGDHc as well as its E1-E2 subcomplex are implicated in neurodegenerative disorders, ischemia-reperfusion injury, E3-deficiency and cancers.We performed cryo-EM, cross-linking mass spectrometry (CL-MS) and molecular modeling analyses to determine the structure of the E2 component of the hKGDHc (hE2k); hE2k transfers a succinyl group to CoA and forms the structural core of hKGDHc. We also assessed the overall structure of the hKGDHc by negative-stain EM and modeling.We report the 2.9 Å resolution cryo-EM structure of the hE2k component. The cryo-EM map comprises density for hE2k residues 151-386 - the entire (inner) core catalytic domain plus a few additional residues -, while residues 1-150 are not observed due to the inherent flexibility of the N-terminal region. The structure of the latter segment was also determined by CL-MS and homology modeling. Negative-stain EM on in vitro assembled hKGDHc and previous data were used to build a putative overall structural model of the hKGDHc.The E2 core of the hKGDHc is composed of 24 hE2k chains organized in octahedral (8 × 3 type) assembly. Each lipoyl domain is oriented towards the core domain of an adjacent chain in the hE2k homotrimer. hE1k and hE3 are most likely tethered at the edges and faces, respectively, of the cubic hE2k assembly.The revealed structural information will support the future pharmacologically targeting of the hKGDHc.},
	keywords = {cryo-electron microscopy; cross-linking mass spectrometry; 2-Oxoglutarate dehydrogenase complex; Dihydrolipoamide succinyltransferase; α-Ketoglutarate dehydrogenase complex},
	year = {2021},
	eissn = {1872-8006},
	orcid-numbers = {Nagy, Bálint/0000-0003-3669-7041; Ozohanics, Olivér/0000-0002-2705-9921; Zámbó, Zsófia Melinda/0000-0001-8657-8556; Szabó, Eszter/0000-0002-9634-2771; Hubert, Ágnes/0000-0001-6452-299X; Ádám, Veronika/0000-0002-8350-8701; Ambrus, Attila/0000-0001-6014-3175}
}

@article{MTMT:33081530,
	title = {Structure of the dihydrolipoamide succinyltransferase (E2) component of the human alpha-ketoglutarate dehydrogenase complex (hKGDHc) revealed by cryo-EM and cross-linking mass spectrometry: Implications for the overall hKGDHc structure},
	url = {https://m2.mtmt.hu/api/publication/33081530},
	author = {Nagy, Bálint and Martin, Polak and Ozohanics, Olivér and Zámbó, Zsófia Melinda and Szabó, Eszter and Hubert, Ágnes and Frank, Jordan and Jiri, Novacek and Ádám, Veronika and Ambrus, Attila},
	doi = {10.1002/pro.4191},
	journal-iso = {PROTEIN SCI},
	journal = {PROTEIN SCIENCE},
	volume = {30},
	unique-id = {33081530},
	issn = {0961-8368},
	year = {2021},
	eissn = {1469-896X},
	pages = {171-171},
	orcid-numbers = {Nagy, Bálint/0000-0003-3669-7041; Ozohanics, Olivér/0000-0002-2705-9921; Zámbó, Zsófia Melinda/0000-0001-8657-8556; Szabó, Eszter/0000-0002-9634-2771; Hubert, Ágnes/0000-0001-6452-299X; Ádám, Veronika/0000-0002-8350-8701; Ambrus, Attila/0000-0001-6014-3175}
}

@mastersthesis{MTMT:31932299,
	title = {A humán dihidrolipoamid-dehidrogenáz patogén mutánsainak szerkezetanalízise},
	url = {https://m2.mtmt.hu/api/publication/31932299},
	author = {Szabó, Eszter},
	doi = {10.14753/SE.2020.2387},
	unique-id = {31932299},
	year = {2020},
	orcid-numbers = {Szabó, Eszter/0000-0002-9634-2771}
}

@article{MTMT:33081442,
	title = {Structure of the Dihydrolipoamide Succinyltransferase (E2) Component of the Human α-ketoglutarate dehydrogenase complex (hKGDHc) revealed by cryo-EM and Cross-linking mass spectrometry: Implications for the overall hKGDHc structure},
	url = {https://m2.mtmt.hu/api/publication/33081442},
	author = {Nagy, Bálint and Polak, Martin and Ozohanics, Olivér and Zámbó, Zsófia Melinda and Szabó, Eszter and Hubert, Ágnes and Jordan, Frank and Novacek, Jiri and Ádám, Veronika and Ambrus, Attila},
	doi = {10.1016/j.freeradbiomed.2020.10.088},
	journal-iso = {FREE RADICAL BIO MED},
	journal = {FREE RADICAL BIOLOGY AND MEDICINE},
	volume = {159},
	unique-id = {33081442},
	issn = {0891-5849},
	year = {2020},
	eissn = {1873-4596},
	pages = {S29-S30},
	orcid-numbers = {Nagy, Bálint/0000-0003-3669-7041; Ozohanics, Olivér/0000-0002-2705-9921; Zámbó, Zsófia Melinda/0000-0001-8657-8556; Szabó, Eszter/0000-0002-9634-2771; Hubert, Ágnes/0000-0001-6452-299X; Ádám, Veronika/0000-0002-8350-8701; Ambrus, Attila/0000-0001-6014-3175}
}

@article{MTMT:30799456,
	title = {Underlying molecular alterations in human dihydrolipoamide dehydrogenase deficiency revealed by structural analyses of disease-causing enzyme variants},
	url = {https://m2.mtmt.hu/api/publication/30799456},
	author = {Szabó, Eszter and Wilk, Piotr and Nagy, Bálint and Zámbó, Zsófia Melinda and Bui, Dávid and Weichsel, Andrzej and Arjunan, Palaniappa and Törőcsik, Beáta and Hubert, Agnes and Furey, William and Montfort, William R and Jordan, Frank and Weiss, Manfred S and Ádám, Veronika and Ambrus, Attila},
	doi = {10.1093/hmg/ddz177},
	journal-iso = {HUM MOL GENET},
	journal = {HUMAN MOLECULAR GENETICS},
	volume = {28},
	unique-id = {30799456},
	issn = {0964-6906},
	abstract = {Human dihydrolipoamide dehydrogenase (hLADH, hE3) deficiency (OMIM# 246900) is an often prematurely lethal genetic disease usually caused by inactive or partially inactive hE3 variants. Here we report the crystal structure of wild-type hE3 at an unprecedented high resolution of 1.75 Å and the structures of six disease-causing hE3 variants at resolutions ranging from 1.44 to 2.34 Å. P453L proved to be the most deleterious substitution in structure as aberrations extensively compromised the active site. The most prevalent G194C-hE3 variant primarily exhibited structural alterations close to the substitution site, whereas the nearby cofactor-binding residues were left unperturbed. The G426E substitution mainly interfered with the local charge distribution introducing dynamics to the substitution site in the dimer interface; G194C and G426E both led to minor structural changes. The R460G, R447G, and I445M substitutions all perturbed a solvent accessible channel, the so-called H+/H2O channel, leading to the active site. Molecular pathomechanisms of enhanced reactive oxygen species (ROS) generation and impaired binding to multienzyme complexes were also addressed according to the structural data for the relevant mutations. In summary, we present here for the first time a comprehensive study that links three-dimensional structures of disease-causing hE3 variants to residual hLADH activities, altered capacities for ROS generation, compromised affinities for multienzyme complexes, and eventually clinical symptoms. Our results may serve as useful starting points for future therapeutic intervention approaches.},
	year = {2019},
	eissn = {1460-2083},
	pages = {3339-3354},
	orcid-numbers = {Szabó, Eszter/0000-0002-9634-2771; Nagy, Bálint/0000-0003-3669-7041; Zámbó, Zsófia Melinda/0000-0001-8657-8556; Bui, Dávid/0000-0003-3726-2031; Törőcsik, Beáta/0000-0002-9838-3710; Ádám, Veronika/0000-0002-8350-8701; Ambrus, Attila/0000-0001-6014-3175}
}