A5036381352- Biochemical Acid Research Studies
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Biochemical and Molecular Research
- DNA and Nucleic Acid Chemistry
- Microbial Metabolic Engineering and Bioproduction
- Alcoholism and Thiamine Deficiency
- Cancer, Hypoxia, and Metabolism
- Advanced biosensing and bioanalysis techniques
- ATP Synthase and ATPases Research
- Diet and metabolism studies
- Blood properties and coagulation
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Muscle metabolism and nutrition
- Electrochemical sensors and biosensors
- Mass Spectrometry Techniques and Applications
- Enzyme Structure and Function
- Rheology and Fluid Dynamics Studies
- Neuroscience and Neuropharmacology Research
- Metal complexes synthesis and properties
- Nitric Oxide and Endothelin Effects
- Diet, Metabolism, and Disease
- Cardiac Ischemia and Reperfusion
- Vitamin C and Antioxidants Research
Semmelweis University
2015-2024
Institute of Biochemistry
2020-2023
Hungarian Academy of Sciences
2008-2011
University of Arizona
2001-2009
Rutgers, The State University of New Jersey
2005-2006
University of Debrecen
2001
Human telomeric DNA consists of tandem repeats the sequence d(TTAGGG).The formation and stabilization G-quadruplexes in human have been shown to inhibit activity telomerase, thus G-quadruplex has considered as an attractive target for cancer therapeutic intervention.However, knowledge intact structure(s) formed under physiological conditions is a prerequisite structure-based rational drug design.Here we report folding structure K 1 solution determined by NMR.Our results demonstrate novel,...
The nuclease hypersensitivity element III1 (NHE III1) of the c-MYC promoter strongly controls transcriptional activity oncogene. purine-rich strand NHE has been shown to be a silencer for transcription upon formation G-quadruplex structure. We have determined predominant structure this in potassium solution by NMR. adopts an intramolecular parallel-stranded quadruplex conformation with three guanine tetrads and side loops, including two single-nucleotide loops one double-nucleotide loop,...
We report the first G-quadruplex structure formed in promoter region of human bcl-2. Bcl-2 is a potent oncoprotein that functions as an inhibitor cell apoptosis and has been found to be aberrantly overexpressed wide range tumors. A highly GC-rich upstream P1 plays important role regulation transcriptional activity bcl-2 oncogene. The purine-rich strand this contains multiple runs guanines can form three distinct intramolecular G-quadruplexes K+-containing solution. Of these, within middle...
We report the NMR solution structure of intramolecular G-quadruplex formed in human telomeric DNA K+. The hybrid-type consists three G-tetrads linked with mixed parallel–antiparallel G-strands, bottom two having same G-arrangement (anti:anti:syn:anti) and top G-tetrad reversed (syn:syn:anti:syn). TTA loop segments adopt different conformations, first assuming a double-chain-reversal conformation, second third lateral conformations. is very well defined, including loops flanking sequences at...
CueO, a multicopper oxidase, is part of the copper-regulatory cue operon in Escherichia coli, expressed under conditions copper stress and shows enhanced oxidase activity when additional present. The 1.7-Å resolution structure crystal soaked CuCl2 reveals Cu(II) ion bound to protein 7.5 Å from T1 site region rich methionine residues. trigonal bipyramidal coordination sphere unusual, containing two sulfur atoms, aspartate carboxylate oxygen water molecule. Asp-439 both ligates labile...
// Hajnalka Harami-Papp 1, * , Lőrinc S. Pongor 3, Gyöngyi Munkácsy 1 Gergő Horváth 2 Ádám M. Nagy Attila Ambrus Péter Hauser 3 András Szabó László Tretter Balázs Győrffy MTA TTK Lendület Cancer Biomarker Research Group, H-1117, Budapest, Hungary Semmelweis University, Department of Medical Biochemistry, H-1094, Second Pediatrics, These authors have contributed equally to this work Correspondence to: Győrffy,...
Abstract Dihydrolipoamide dehydrogenase (LADH) is a flavo‐enzyme that serves as subunit of α‐ketoglutarate complex (α‐KGDHC). Reactive oxygen species (ROS) generation by α‐KGDHC has been assigned to LADH (E3 subunit) and explained the diaphorase activity E3. Dysfunctions concurrent ROS production have implicated in neurodegeneration, ischemia‐reperfusion, other pathological conditions. In this work we investigated in‐depth details isolated α‐KGDHC. We found parallel superoxide hydrogen...
We investigated pathogenic mutations relevant in dihydrolipoamide dehydrogenase (LADH; gene: Dld) deficiency, a severe human disease, to elucidate how they alter reactive oxygen species (ROS) generation and associated biophysical characteristics of LADH. Twelve known disease-causing mutants LADH have been expressed purified homogeneity from E. coli. Detailed biochemical characterization the has performed applying circular dichroism (CD) spectroscopy, nano-spray mass spectrometry (MS),...
Herein are reported unique properties of the human 2-oxoglutarate dehydrogenase multienzyme complex (OGDHc), a rate-limiting enzyme in Krebs (citric acid) cycle. (a) Functionally competent (E1o-h) and dihydrolipoyl succinyltransferase components have been expressed according to kinetic spectroscopic evidence. (b) A stable free radical, consistent with C2-(C2α-hydroxy)-γ-carboxypropylidene thiamin diphosphate (ThDP) cation radical was detected by electron spin resonance upon reaction E1o-h...
The human mitochondrial alpha-ketoglutarate dehydrogenase complex (hKGDHc) converts KG to succinyl-CoA and NADH. Malfunction of reactive oxygen species generation by the hKGDHc as well its E1-E2 subcomplex are implicated in neurodegenerative disorders, ischemia-reperfusion injury, E3-deficiency cancers.We performed cryo-EM, cross-linking mass spectrometry (CL-MS) molecular modeling analyses determine structure E2 component (hE2k); hE2k transfers a succinyl group CoA forms structural core...
I-motifs are four-stranded DNA secondary structures formed in C-rich sequences and consist of parallel-stranded duplexes zipped together an antiparallel orientation by intercalated, hemiprotonated cytosine+−cytosine base pairs. I-motif have been indicated to form various regions the human genome as well nanotechnological applications. While NMR is a major tool for structural studies I-motifs, determination folding topologies unimolecular has challenging arduous task using conventional...
The human 2-oxoglutaric acid dehydrogenase complex (hOGDHc) plays a pivotal role in the tricarboxylic (TCA) cycle, and its diminished activity is associated with neurodegenerative diseases. hOGDHc comprises three components, hE1o, hE2o, hE3, we recently reported functionally active E1o E2o enabling studies on their assembly. No atomic-resolution structure for hE2o component currently available, so here first studied interactions binary subcomplexes (hE1o–hE2o, hE1o–hE3, hE2o–hE3) to gain...
Succinate-driven reverse electron transport (RET) is one of the main sources mitochondrial reactive oxygen species (mtROS) in ischemia-reperfusion injury. RET dependent on membrane potential (Δψm) and transmembrane pH difference (ΔpH), components proton motive force (pmf); a decrease Δψm and/or ΔpH inhibits RET. In this study we aimed to determine which component pmf displays more dominant effect RET-provoked ROS generation isolated guinea pig brain heart mitochondria respiring succinate or...
The human 2-oxoglutarate dehydrogenase complex (hOGDHc) is a key enzyme in the tricarboxylic acid cycle and one of main regulators mitochondrial metabolism through NADH reactive oxygen species levels. Evidence was obtained for formation hybrid between hOGDHc its homologue 2-oxoadipate (hOADHc) L-lysine metabolic pathway, suggesting crosstalk two distinct pathways. Findings raised fundamental questions about assembly hE1a (2-oxoadipate-dependent E1 component) hE1o (2-oxoglutarate-dependent...
Human dihydrolipoamide dehydrogenase (hLADH, hE3) deficiency (OMIM# 246900) is an often prematurely lethal genetic disease usually caused by inactive or partially hE3 variants. Here we report the crystal structure of wild-type at unprecedented high resolution 1.75 Å and structures six disease-causing variants resolutions ranging from 1.44 to 2.34 Å. P453L proved be most deleterious substitution in as aberrations extensively compromised active site. The prevalent G194C-hE3 variant primarily...
α-ketoglutarate dehydrogenase complex (KGDHc), or 2-oxoglutarate (OGDHc) is a rate-limiting enzyme in the tricarboxylic acid cycle, that has been identified neurodegenerative diseases such as Alzheimer's disease. The aim of present study was to establish role KGDHc and its subunits bioenergetics reactive oxygen species (ROS) homeostasis brain mitochondria. To bioenergetic profile KGDHc, genetically modified mouse strains were used having heterozygous knock out (KO) either dihydrolipoyl...
Abstract The ketoglutarate dehydrogenase complex (KGDHC) consists of three different subunits encoded by OGDH (or OGDHL ), DLST, and DLD , combined in stoichiometries. subunit is shared between KGDHC pyruvate complex, branched-chain alpha-keto acid the glycine cleavage system. Despite KGDHC’s implication neurodegenerative diseases, cell-specific localization its adult human brain has never been investigated. Here, we show that immunoreactivity all known isoforms OGDHL, OGDH, DLST was...