TY - JOUR AU - Kelemen, Ádám András AU - Perczel, András AU - Horváth, Dániel AU - Jákli, Imre TI - Amide isomerization pathways: Electronic and structural background of protonation- and deprotonation-mediated cis-trans interconversions JF - JOURNAL OF CHEMICAL PHYSICS J2 - J CHEM PHYS VL - 159 PY - 2023 IS - 15 PG - 16 SN - 0021-9606 DO - 10.1063/5.0165772 UR - https://m2.mtmt.hu/api/publication/34199131 ID - 34199131 AB - The cis-trans isomerization of amide bonds leads to wide range of structural and functional changes in proteins and can easily be the rate-limiting step in folding. The trans isomer is thermodynamically more stable than the cis, nevertheless the cis form can play a role in biopolymers’ function. The molecular system of N-methylacetamide · 2H2O is complex enough to reveal energetics of the cis-trans isomerization at coupled cluster single-double and coupled cluster single–double and perturbative triple [CCSD(T)] levels of theory. The cis-trans isomerization cannot be oversimplified by a rotation along ω, since this rotation is coupled with the N-atom pyramidal inversion, requesting the introduction of a second dihedral angle “α.” Full f(ω,α) potential energy surfaces of the different amide protonation states, critical points and isomerization reaction paths were determined, and the barriers of the neutral, O-protonated and N-deprotonated amides were found too high to allow cis-trans interconversion at room temperature: ∼85, ∼140, and ∼110 kJ mol−1, respectively. For the N-protonated amide bond, the cis form (ω = 0°) is a maximum rather than a minimum, and each ω state is accessible for less than ∼10 kJ mol−1. Here we outline a cis-trans isomerization pathway with a previously undescribed low energy transition state, which suggests that the proton is transferred from the more favorable O- to the N-protonation site with the aid of nearby water molecules, allowing the trans → cis transition to occur at an energy cost of ≤11.6 kJ mol−1. Our results help to explain why isomerase enzymes operate via protonated amide bonds and how N-protonation of the peptide bond occurs via O-protonation. LA - English DB - MTMT ER - TY - JOUR AU - Kiss-Szemán, Anna Júlia AU - Takács, Luca AU - Orgován, Zoltán AU - Stráner, Pál AU - Jákli, Imre AU - Schlosser, Gitta (Vácziné) AU - Masiulis, Simonas AU - Harmat, Veronika AU - Karancsiné Menyhárd, Dóra AU - Perczel, András TI - A carbapenem antibiotic inhibiting a mammalian serine protease: structure of the acylaminoacyl peptidase–meropenem complex JF - CHEMICAL SCIENCE J2 - CHEM SCI VL - 13 PY - 2022 IS - 48 SP - 14264 EP - 14276 PG - 13 SN - 2041-6520 DO - 10.1039/D2SC05520A UR - https://m2.mtmt.hu/api/publication/33307131 ID - 33307131 N1 - Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány Péter sétány 1/A, Budapest, Hungary Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Budapest, Hungary ELKH-ELTE Protein Modelling Research Group, Eötvös Loránd Research Network, Budapest, Hungary ELKH-ELTE Lendület Ion Mobility Mass Spectrometry Research Group, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary Materials and Structural Analysis Division, Thermo Fisher Scientific, Eindhoven, Netherlands Export Date: 28 March 2023 CODEN: CSHCC Correspondence Address: Harmat, V.; Laboratory of Structural Chemistry and Biology, Pázmány Péter sétány 1/A, Hungary; email: veronika.harmat@ttk.elte.hu Correspondence Address: Menyhárd, D.K.; Laboratory of Structural Chemistry and Biology, Pázmány Péter sétány 1/A, Hungary; email: dora.k.menyhard@ttk.elte.hu Correspondence Address: Perczel, A.; Laboratory of Structural Chemistry and Biology, Pázmány Péter sétány 1/A, Hungary; email: perczel.andras@ttk.elte.hu AB - The structure of porcine AAP (pAAP) in a covalently bound complex with meropenem was determined by cryo-EM to 2.1 Å resolution, showing the mammalian serine-protease inhibited by a carbapenem antibiotic. LA - English DB - MTMT ER - TY - JOUR AU - Kiss-Szemán, Anna Júlia AU - Stráner, Pál AU - Jákli, Imre AU - Hosogi, Naoki AU - Harmat, Veronika AU - Karancsiné Menyhárd, Dóra AU - Perczel, András TI - Cryo-EM structure of acylpeptide hydrolase reveals substrate selection by multimerization and a multi-state serine-protease triad JF - CHEMICAL SCIENCE J2 - CHEM SCI VL - 13 PY - 2022 IS - 24 SP - 7132 EP - 7142 PG - 11 SN - 2041-6520 DO - 10.1039/D2SC02276A UR - https://m2.mtmt.hu/api/publication/32830377 ID - 32830377 N1 - Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Budapest, 1117, Hungary MTA-ELTE Protein Modelling Research Group, Eötvös Loránd Research Network, Budapest, 1117, Hungary EM Application Department, EM Business Unit, JEOL Ltd, Tokyo, 196-8556, Japan Cited By :1 Export Date: 28 March 2023 CODEN: CSHCC Correspondence Address: Menyhárd, D.K.; Laboratory of Structural Chemistry and Biology, Hungary; email: dora.k.menyhard@ttk.elte.hu Correspondence Address: Perczel, A.; Laboratory of Structural Chemistry and Biology, Hungary; email: perczel.andras@ttk.elte.hu LA - English DB - MTMT ER - TY - JOUR AU - Láng, András AU - Jákli, Imre AU - Enyedi, Kata Nóra AU - Mező, Gábor AU - Karancsiné Menyhárd, Dóra AU - Perczel, András TI - Off-pathway 3D-structure provides protection against spontaneous Asn/Asp isomerization: shielding proteins Achilles heel JF - QUARTERLY REVIEWS OF BIOPHYSICS J2 - Q REV BIOPHYS VL - 53 PY - 2020 SN - 0033-5835 DO - 10.1017/S003358351900009X UR - https://m2.mtmt.hu/api/publication/31154881 ID - 31154881 N1 - Funding Agency and Grant Number: European UnionEuropean Commission; State of Hungary; European Regional Development FundEuropean Commission [VEKOP-2.3.3-15-2016-00009, VEKOP-2.3.2-16-2017-00014]; NKFIH of the Hungarian Academy of SciencesNational Research, Development & Innovation Office (NRDIO) - Hungary [K116305 OTKA] Funding text: The authors thank Viktor Farkas and Berill nodi for the WVVW hairpin and Pal Straner for the mini protein model, Masashi Yokochi for the BMRB data, and Ern Keszei and Laszlo Nyitray for scientific discussion. NMR spectrometer measurement time (700 MHz Bruker) was the courtesy of MedInProt Grant Facilitating Access to Instruments from the Hungarian Academy of Sciences. Calculations were carried out at the NIIF Supercomputing Center of KIFU (Hungary). This research project was supported by the European Union and the State of Hungary and co-financed by the European Regional Development Fund (VEKOP-2.3.3-15-2016-00009 and VEKOP-2.3.2-16-2017-00014), and the K116305 OTKA grant of the NKFIH of the Hungarian Academy of Sciences. LA - English DB - MTMT ER - TY - CHAP AU - Farkas, Viktor AU - Jákli, Imre AU - Kardos, József AU - Vass, Elemér ED - Buday, László ED - Nyitray, László ED - Perczel, András TI - Elektron- és rezgési spektroszkópia a fehérjekutatásban T2 - Ezerarcú fehérjék PB - Semmelweis Kiadó és Multimédia Stúdió CY - Budapest SN - 9789633314586 PY - 2018 SP - 277 EP - 300 PG - 24 UR - https://m2.mtmt.hu/api/publication/30805932 ID - 30805932 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Karancsiné Menyhárd, Dóra AU - Hudaky, I AU - Jákli, Imre AU - Juhasz, G AU - Perczel, András TI - Predictable Conformational Diversity in Foldamers of Sugar Amino Acids JF - JOURNAL OF CHEMICAL INFORMATION AND MODELING J2 - J CHEM INF MODEL VL - 57 PY - 2017 IS - 4 SP - 757 EP - 768 PG - 12 SN - 1549-9596 DO - 10.1021/acs.jcim.6b00488 UR - https://m2.mtmt.hu/api/publication/3239373 ID - 3239373 N1 - Funding Agency and Grant Number: Hungarian National Science Fund (OTKA)Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [NK101072, K116305] Funding text: This work was supported by grants from the Hungarian National Science Fund (OTKA) (NK101072 and K116305). AB - A systematic conformational search was carried out for monomers and homohexamers of furanoid beta-amino, acids: cis-(S,R) and trans-(S,S) stereoisomers of aminocyclopentane carboxylic acid (ACPC), two different.aniinofuranuronic acids (AFU(alpha) and AFU(beta)), their isopropylidene derivatives (AFU(ip)), and the key intermediate beta-aminotetrahydrofurancarboxylic acid (ATFC). The stereochemistry of the building blocks was chosen to match that of the natural sugar amino acid (xylose and ribose) precursors (XylAFU and RibAFU). The results show that hexamera of cis-furanoid beta-amino acids show great variability: while hydrophobic.cyclopentane (cis-ACPC)(6) and hydrophilic (XylAFU(alpha/beta))(6) foldamers favor two different zigzagged conformation as hexaMers, the backbone fold turns into a helix in the case of (cis-ATFC)(6) (10 -helix) and (XylAFU(ip))(6) (14 -helix). Trans stereochemistry resulted in hexamers exclusively with the right-handed, helix conformation, (H-12(P))(6), regardless of their polarity. We found that the preferred.oligomeric structure of XylAFU(alpha/beta) is conformationally compatible 'with beta-pleated sheets, while that of the trans/(S,S) units matches with alpha-helices of proteins. LA - English DB - MTMT ER - TY - JOUR AU - Papp, Dóra AU - Petra, Rovó AU - Jákli, Imre AU - Császár, Attila Géza AU - Perczel, András TI - Four Faces of the Interaction between Ions and Aromatic Rings JF - JOURNAL OF COMPUTATIONAL CHEMISTRY J2 - J COMPUT CHEM VL - 38 PY - 2017 IS - 20 SP - 1762 EP - 1773 PG - 12 SN - 0192-8651 DO - 10.1002/jcc.24816 UR - https://m2.mtmt.hu/api/publication/3229927 ID - 3229927 N1 - Funding Agency and Grant Number: NKFIH [K119658, NK101072] Funding text: Contract grant sponsor: NKFIH; Contract grant numbers: K119658 (to A.G.C.) and NK101072 (to A.P.) LA - English DB - MTMT ER - TY - JOUR AU - Farkas, Viktor AU - Jákli, Imre AU - Tóth, Gábor AU - Perczel, András TI - Aromatic Cluster Sensor of Protein Folding: Near-UV Electronic Circular Dichroism Bands Assigned to Fold Compactness JF - CHEMISTRY-A EUROPEAN JOURNAL J2 - CHEM-EUR J VL - 22 PY - 2016 IS - 39 SP - 13871 EP - 13883 PG - 13 SN - 0947-6539 DO - 10.1002/chem.201602455 UR - https://m2.mtmt.hu/api/publication/3101105 ID - 3101105 N1 - MTA-ELTE Protein Modelling Research Group, Eötvös Loránd University, Pázmány P. sétány 1A, Budapest, 1117, Hungary Department of Medical Chemistry, University of Szeged, Dóm tér 8, Szeged, 6720, Hungary Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány P. sétány 1A, Budapest, 1117, Hungary Cited By :2 Export Date: 18 September 2019 CODEN: CEUJE Correspondence Address: Perczel, A.; MTA-ELTE Protein Modelling Research Group, Eötvös Loránd University, Pázmány P. sétány 1A, Hungary; email: perczel@chem.elte.hu Funding Agency and Grant Number: iNext; Hungarian National Science Fund (OTKA)Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [NK101072] Funding text: Comments and critics of A. Lang and P. Rovo are highly appreciated. This work was supported by grants from iNext and the Hungarian National Science Fund (OTKA, NK101072). AB - Both far- and near-UV electronic circular dichroism (ECD) spectra have bands sensitive to thermal unfolding of Trp and Tyr residues containing proteins. Beside spectral changes at 222nm reporting secondary structural variations (far-UV range), Lb bands (near-UV range) are applicable as 3D-fold sensors of protein's core structure. In this study we show that both Lb(Tyr) and Lb(Trp) ECD bands could be used as sensors of fold compactness. ECD is a relative method and thus requires NMR referencing and cross-validation, also provided here. The ensemble of 204 ECD spectra of Trp-cage miniproteins is analysed as a training set for "calibrating" Trp↔Tyr folded systems of known NMR structure. While in the far-UV ECD spectra changes are linear as a function of the temperature, near-UV ECD data indicate a non-linear and thus, cooperative unfolding mechanism of these proteins. Ensemble of ECD spectra deconvoluted gives both conformational weights and insight to a protein folding↔unfolding mechanism. We found that the Lb 293 band is reporting on the 3D-structure compactness. In addition, the pure near-UV ECD spectrum of the unfolded state is described here for the first time. Thus, ECD folding information now validated can be applied with confidence in a large thermal window (5≤T≤85°C) compared to NMR for studying the unfolding of Trp↔Tyr residue pairs. In conclusion, folding propensities of important proteins (RNA polymerase II, ubiquitin protein ligase, tryptase-inhibitor etc.) can now be analysed with higher confidence. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. LA - English DB - MTMT ER - TY - JOUR AU - Goldschmidt Gőz, Viktória AU - Pintér, István AU - Csámpai, Antal AU - Jákli, Imre AU - Zsoldos-Mády, Virág AU - Perczel, András TI - Hydrogen-Bonding Network Anchors the Cyclic Form of Sugar Arylhydrazones JF - EUROPEAN JOURNAL OF ORGANIC CHEMISTRY J2 - EUR J ORG CHEM VL - 2016 PY - 2016 IS - 20 SP - 3419 EP - 3426 PG - 8 SN - 1434-193X DO - 10.1002/ejoc.201600462 UR - https://m2.mtmt.hu/api/publication/3091952 ID - 3091952 AB - The "classical" challenge, raised by Emil Fischer as to why one monosaccharide arylhydrazone adopts a cyclic structure but another an acyclic structure, is answered here. The present comprehensive analysis of hexose and hexosamine arylhydrazones, based on 2D NMR spectroscopy and theoretical modeling, has established that the chain of hydrogen bonds needed for conformational selection can only be completed for d-glucosamine derivatives. Thus, d-glucosamine 4-nitrophenylhydrazone exclusively adopts its cyclic form, but any configurational changes imply the formation of acyclic structures. In conclusion, three criteria dominate structure selection, namely 1) an amino function at the C-2 position, 2) the "all-equatorial" substitution mode of the pyranoid ring, and 3) an electron-withdrawing group on the arylhydrazone are all needed to get the cyclic form only. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. LA - English DB - MTMT ER - TY - JOUR AU - Gerlei, KZ AU - Élo, L AU - Fiser, Béla AU - Owen, Michael Christopher AU - Jákli, Imre AU - Knak, Jensen SJ AU - Csizmadia, Imre Gyula AU - Perczel, András AU - Viskolcz, Béla TI - Impairment of a model peptide by oxidative stress: Thermodynamic stabilities of asparagine diamide Cα-radical foldamers JF - CHEMICAL PHYSICS LETTERS J2 - CHEM PHYS LETT VL - 593 PY - 2014 SP - 104 EP - 108 PG - 5 SN - 0009-2614 DO - 10.1016/j.cplett.2013.12.037 UR - https://m2.mtmt.hu/api/publication/2553691 ID - 2553691 AB - Electron structure calculations on N-acetyl asparagine N-methylamide were performed to identify the global minimum from which radicals were formed after H-abstraction by the OH radical. It was found that the radical generated by breaking the C-H bond of the α-carbon was thermodynamically the most stable one in the gas- and aqueous phases. The extended (βL and βD) backbone conformations are the most stable, but syn-syn or inverse γ-turn (γL) and γ-turn (γ D) have substantial stability too. The highest energy conformers are the degenerate εL and εD foldamers. Clearly, the most stable β foldamer is the most likely intermediate for racemization. © 2013 Elsevier B.V. All rights reserved. LA - English DB - MTMT ER -