@article{MTMT:30611881, title = {Ligand entry in human ileal bile acid-binding protein is mediated by histidine protonation}, url = {https://m2.mtmt.hu/api/publication/30611881}, author = {Horváth, Gergő and Lejtoviczné Egyed, Orsolya and Tang, Changguo and Kovács, Mihály and Micsonai, András and Kardos, József and Tőke, Orsolya}, doi = {10.1038/s41598-019-41180-7}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {9}, unique-id = {30611881}, issn = {2045-2322}, year = {2019}, eissn = {2045-2322}, orcid-numbers = {Kovács, Mihály/0000-0002-1200-4741; Micsonai, András/0000-0002-2539-4080; Kardos, József/0000-0002-2135-2932} } @mastersthesis{MTMT:3071512, title = {Belső molekuláris mozgások vizsgálata a humán epesav-kötő fehérjében NMR-spektroszkópiával}, url = {https://m2.mtmt.hu/api/publication/3071512}, author = {Horváth, Gergő}, doi = {10.15476/ELTE.2015.113}, publisher = {Eötvös Loránd University}, unique-id = {3071512}, keywords = {BIOKÉMIA; NMR spektroszkópia; lipidkötő fehérje; epesavkötő fehérje}, year = {2016} } @article{MTMT:3048907, title = {Structural determinants of ligand binding in the ternary complex of human ileal bile acid binding protein with glycocholate and glycochenodeoxycholate obtained from solution NMR.}, url = {https://m2.mtmt.hu/api/publication/3048907}, author = {Horváth, Gergő and Bencsura, Ákos and Simon, Ágnes and Tochtrop, GP and DeKoster, GT and Covey, DF and Cistola, DP and Tőke, Orsolya}, doi = {10.1111/febs.13610}, journal-iso = {FEBS J}, journal = {FEBS JOURNAL}, volume = {283}, unique-id = {3048907}, issn = {1742-464X}, abstract = {Besides aiding digestion, bile salts are important signal molecules exhibiting a regulatory role in metabolic processes. Human ileal bile acid binding protein (I-BABP) is an intracellular carrier of bile salts in the epithelial cells of the distal small intestine and has a key role in the enterohepatic circulation of bile salts. Positive binding cooperativity combined with site selectivity of glycocholate and glycochenodeoxycholate, the two most abundant bile salts in the human body, make human I-BABP a unique member of the family of intracellular lipid binding proteins. Solution NMR structure of the ternary complex of human I-BABP with glycocholate and glycochenodeoxycholate reveals an extensive network of hydrogen bonds and hydrophobic interactions stabilizing the bound bile salts. Conformational changes accompanying bile salt binding affects four major regions in the protein including the C/D, E/F and G/H loops as well as the helical segment. Most of these protein regions coincide with a previously described network of millisecond time scale fluctuations in the apo protein, a motion absent in the bound state. Comparison of the heterotypic doubly ligated complex with the unligated form provides further evidence of a conformation selection mechanism of ligand entry. Structural and dynamic aspects of human I-BABP-bile salt interaction are discussed and compared with characteristics of ligand binding in other members of the intracellular lipid binding protein family. PROTEIN DATA BANK ACCESSION NUMBERS: The coordinates of the 10 lowest energy structures of the human I-BABP : GCDA : GCA complex as well as the distance restraints used to calculate the final ensemble have been deposited in the Brookhaven Protein Data Bank with accession number 2MM3.}, year = {2016}, eissn = {1742-4658}, pages = {541-555} } @article{MTMT:2749407, title = {Temperature Dependence of Backbone Dynamics in Human Ileal Bile Acid-Binding Protein: Implications for the Mechanism of Ligand Binding}, url = {https://m2.mtmt.hu/api/publication/2749407}, author = {Horváth, Gergő and Lejtoviczné Egyed, Orsolya and Tőke, Orsolya}, doi = {10.1021/bi500553f}, journal-iso = {BIOCHEMISTRY-US}, journal = {BIOCHEMISTRY}, volume = {53}, unique-id = {2749407}, issn = {0006-2960}, abstract = {Human ileal bile acid-binding protein (I-BABP), a member of the family of intracellular lipid binding proteins plays a key role in the cellular trafficking and metabolic regulation of bile salts. The protein has two internal and, according to a recent study, an additional superficial binding site and binds di- and trihydroxy bile salts with positive cooperativity and a high degree of site-selectivity. Previously, in the apo form, we have identified an extensive network of conformational fluctuations on the millisecond time scale, which cease upon ligation. Additionally, ligand binding at room temperature was found to be accompanied by a slight rigidification of picosecond-nanosecond (ps-ns) backbone flexibility. In the current study, temperature-dependent N-15 NMR spin relaxation measurements were used to gain more insight into the role of dynamics in human I-BABP-bile salt recognition. According to our analysis, residues sensing a conformational exchange in the apo state can be grouped into two clusters with slightly different exchange rates. The entropy-enthalpy compensation observed for both clusters suggests a disorder-order transition between a ground and a sparsely populated higher energy state in the absence of ligands. Analysis of the faster, ps-ns motion of N-15-H-1 bond vectors indicates an unusual nonlinear temperature-dependence for both ligation states. Intriguingly, while bile salt binding results in a more uniform response to temperature change throughout the protein, the temperature derivative of the generalized order parameter shows different responses to temperature increase for the two forms of the protein in the investigated temperature range. Analysis of both slow and fast motions in human I-BABP indicates largely different energy landscapes for the apo and halo states suggesting that optimization of binding interactions might be achieved by altering the dynamic behavior of specific segments in the protein.}, keywords = {COOPERATIVITY; MODEL-FREE APPROACH; EXCHANGE; MAGNETIC-RESONANCE RELAXATION; FATTY-ACID; ORDER PARAMETERS; CONFORMATIONAL ENTROPY; TIME-SCALE DYNAMICS; SITE-SPECIFIC BINDING; HETERONUCLEAR NMR-SPECTROSCOPY}, year = {2014}, eissn = {1520-4995}, pages = {5186-5198} } @article{MTMT:2305528, title = {Sodium selective ion channel formation in living cell membranes by polyamidoamine dendrimer}, url = {https://m2.mtmt.hu/api/publication/2305528}, author = {Nyitrai, Gabriella and Keszthelyi, Tamás and Bóta, Attila and Simon, Ágnes and Tőke, Orsolya and Horváth, Gergő and Pál, Ildikó and Kardos, Julianna and Héja, László}, doi = {10.1016/j.bbamem.2013.04.004}, journal-iso = {BBA-BIOMEMBRANES}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES}, volume = {1828}, unique-id = {2305528}, issn = {0005-2736}, year = {2013}, eissn = {1879-2642}, pages = {1873-1880}, orcid-numbers = {Pál, Ildikó/0000-0003-2124-9967} } @article{MTMT:1858840, title = {Internal motions and exchange processes in human ileal bile acid-binding protein as studied by backbone ^^15^^^N NMR spectroscopy}, url = {https://m2.mtmt.hu/api/publication/1858840}, author = {Horváth, Gergő and Király, Péter and Tárkányi, Gábor and Tőke, Orsolya}, doi = {10.1021/bi201588q}, journal-iso = {BIOCHEMISTRY-US}, journal = {BIOCHEMISTRY}, volume = {51}, unique-id = {1858840}, issn = {0006-2960}, year = {2012}, eissn = {1520-4995}, pages = {1848-1861} }