TY - JOUR AU - Horváth, Gergő AU - Lejtoviczné Egyed, Orsolya AU - Tang, Changguo AU - Kovács, Mihály AU - Micsonai, András AU - Kardos, József AU - Tőke, Orsolya TI - Ligand entry in human ileal bile acid-binding protein is mediated by histidine protonation JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 9 PY - 2019 PG - 17 SN - 2045-2322 DO - 10.1038/s41598-019-41180-7 UR - https://m2.mtmt.hu/api/publication/30611881 ID - 30611881 N1 - Laboratory for NMR Spectroscopy, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 2 Magyar tudósok körútja, Budapest, H-1117, Hungary Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, United States Department of Biochemistry, ELTE-MTA “Momentum” Motor Enzymology Research Group, Eötvös Loránd University, Pázmány Péter sétány 1/C, Budapest, H-1117, Hungary Department of Biochemistry, MTA-ELTE NAP B Neuroimmunology Research Group, Institute of Biology, Eötvös Loránd University, Pázmány Péter sétány 1/C, Budapest, H-1117, Hungary Export Date: 9 July 2019 Correspondence Address: Toke, O.; Laboratory for NMR Spectroscopy, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 2 Magyar tudósok körútja, Hungary; email: toke.orsolya@ttk.mta.hu LA - English DB - MTMT ER - TY - THES AU - Horváth, Gergő TI - Belső molekuláris mozgások vizsgálata a humán epesav-kötő fehérjében NMR-spektroszkópiával PB - Eötvös Loránd Tudományegyetem (ELTE) PY - 2016 SP - 98 DO - 10.15476/ELTE.2015.113 UR - https://m2.mtmt.hu/api/publication/3071512 ID - 3071512 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Horváth, Gergő AU - Bencsura, Ákos AU - Simon, Ágnes AU - Tochtrop, GP AU - DeKoster, GT AU - Covey, DF AU - Cistola, DP AU - Tőke, Orsolya TI - Structural determinants of ligand binding in the ternary complex of human ileal bile acid binding protein with glycocholate and glycochenodeoxycholate obtained from solution NMR. JF - FEBS JOURNAL J2 - FEBS J VL - 283 ET - 0 PY - 2016 IS - 3 SP - 541 EP - 555 PG - 15 SN - 1742-464X DO - 10.1111/febs.13610 UR - https://m2.mtmt.hu/api/publication/3048907 ID - 3048907 N1 - Institute of Organic Chemistry, Research Centre for Natural Sciences Hungarian Academy of Sciences, 2 Magyar tudósok kïrutja, Budapest, H-1117, Hungary Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO, United States Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO, United States Cited By :12 Export Date: 29 November 2021 CODEN: FJEOA Correspondence Address: Toke, O.; Institute of Organic Chemistry, 2 Magyar tudósok kïrutja, Hungary; email: toke.orsolya@ttk.mta.hu Chemicals/CAS: glycochenodeoxycholic acid, 640-79-9; glycocholic acid, 475-31-0; carrier protein, 80700-39-6; bile acid binding proteins; Carrier Proteins; Glycochenodeoxycholic Acid; Glycocholic Acid; Ligands; Membrane Glycoproteins; Solutions Funding details: National Institute of Diabetes and Digestive and Kidney Diseases, NIDDK, R01DK048046 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Horváth, Gergő AU - Lejtoviczné Egyed, Orsolya AU - Tőke, Orsolya TI - Temperature Dependence of Backbone Dynamics in Human Ileal Bile Acid-Binding Protein: Implications for the Mechanism of Ligand Binding JF - BIOCHEMISTRY J2 - BIOCHEMISTRY-US VL - 53 PY - 2014 IS - 31 SP - 5186 EP - 5198 PG - 13 SN - 0006-2960 DO - 10.1021/bi500553f UR - https://m2.mtmt.hu/api/publication/2749407 ID - 2749407 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Nyitrai, Gabriella AU - Keszthelyi, Tamás AU - Bóta, Attila AU - Simon, Ágnes AU - Tőke, Orsolya AU - Horváth, Gergő AU - Pál, Ildikó AU - Kardos, Julianna AU - Héja, László TI - Sodium selective ion channel formation in living cell membranes by polyamidoamine dendrimer JF - BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES J2 - BBA-BIOMEMBRANES VL - 1828 PY - 2013 IS - 8 SP - 1873 EP - 1880 PG - 8 SN - 0005-2736 DO - 10.1016/j.bbamem.2013.04.004 UR - https://m2.mtmt.hu/api/publication/2305528 ID - 2305528 N1 - Megjegyzés-23246857 N1 : Chemicals/CAScalcium ion, 14127-61-8; dipalmitoylphosphatidylcholine, 2644-64-6; silicon dioxide, 10279-57-9, 14464-46-1, 14808-60-7, 15468-32-3, 60676-86-0, 7631-86-9; sodium ion, 17341-25-2 LA - English DB - MTMT ER - TY - JOUR AU - Horváth, Gergő AU - Király, Péter AU - Tárkányi, Gábor AU - Tőke, Orsolya TI - Internal motions and exchange processes in human ileal bile acid-binding protein as studied by backbone ^^15^^^N NMR spectroscopy JF - BIOCHEMISTRY J2 - BIOCHEMISTRY-US VL - 51 PY - 2012 SP - 1848 EP - 1861 PG - 14 SN - 0006-2960 DO - 10.1021/bi201588q UR - https://m2.mtmt.hu/api/publication/1858840 ID - 1858840 LA - English DB - MTMT ER -