Article
Biochemistry & Molecular Biology
Laura E. Sperl, Florian Ruehrnoessl, Anita Schiller, Martin Haslbeck, Franz Hagn
Summary: The study used NMR and HDX-MS techniques in lipid nanodiscs to investigate the high-resolution structural changes of Bak in a membrane environment, providing important insights into Bak-mediated membrane permeabilization. Experimental results showed that the alpha-helix 1 element in Bak is a metastable structure contributing to its pro-apoptotic features.
Article
Biochemistry & Molecular Biology
Melina Daniilidis, Matthias J. Brandl, Franz Hagn
Summary: Membrane mimetics play a crucial role in studying the structure and function of membrane proteins. In this study, the authors compared the biophysical properties of circularized and linear nanodiscs and found that circularized nanodiscs have improved membrane fluidity and size stability, making them advantageous for high-resolution NMR studies at elevated temperatures.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Bankala Krishnarjuna, Thirupathi Ravula, Edgar M. Faison, Marco Tonelli, Qi Zhang, Ayyalusamy Ramamoorthy
Summary: In this study, polymer-based nanodiscs were used to measure RDCs from nucleic acids. The nanodiscs were characterized and their alignment stability was confirmed. RDCs from a labeled nucleic acid molecule were successfully measured using the aligned nanodiscs. This demonstrates the potential of SMA-EA-based lipid-nanodiscs for structural and dynamical studies of nucleic acids.
Review
Biochemistry & Molecular Biology
Saman Majeed, Akram Bani Ahmad, Ujala Sehar, Elka R. Georgieva
Summary: Integral membrane proteins play crucial roles in cell physiology, but mutations and environmental factors can lead to dysfunctional IMPs. Understanding the mechanisms of IMP function and malfunction at the molecular level is essential for advancing our knowledge of cellular physiology and facilitating pharmaceutical developments. In vitro studies using membrane mimetics provide valuable insights into IMP structure and function dynamics.
Article
Biochemistry & Molecular Biology
Erick J. Dufourc
Summary: Membrane nanoobjects such as Bicelles and Nanodiscs are important tools for studying biomembrane properties, providing various membranous platforms for structural biology research. Internal dynamics of these nanoobjects is similar to liposomes, offering potential for studying the 3D structure, topology, and dynamics of membrane proteins.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Biochemistry & Molecular Biology
Martin Jakubec, Espen Barias, Samuel Furse, Morten L. Govasli, Vinnit George, Diana Turcu, Igor A. Iashchishyn, Ludmilla A. Morozova-Roche, Oyvind Halskau
Summary: Research suggests that cholesterol may play a role in the pathogenesis of Parkinson's disease by influencing the binding and fibrillation processes of α-Syn with lipids. The addition of cholesterol can inhibit the interaction between α-Syn and lipid bilayers and significantly promote fibrillation.
Article
Biochemistry & Molecular Biology
Canyong Guo, Lingyun Yang, Zhijun Liu, Dongsheng Liu, Kurt Wuthrich
Summary: Eight hundred and twenty-six human G protein-coupled receptors (GPCRs) play a significant role in mediating the actions of hormones, neurotransmitters, and drugs. Studying the structure and dynamics of GPCRs in lipid bilayer environments is crucial for understanding their functionality and developing new drugs. This study incorporates the A(2A) adenosine receptor into lipid nanodiscs, providing a detergent-free environment for structural studies using NMR. The findings demonstrate the stability and mimicry of the lipid nanodisc and LMNG/CHS micelles in preserving the overall fold and local structure of the receptor.
Article
Chemistry, Multidisciplinary
Meifang Yang, Weiling Luo, Wei Zhang, Huixia Wang, Dongxiang Xue, Yiran Wu, Suwen Zhao, Fei Zhao, Xing Zheng, Houchao Tao
Summary: We report a new strategy based on Ugi reaction for the rapid expansion of detergent diversity. The new detergents were comprehensively evaluated in terms of physical properties and thermal stabilization, and were applied in the study of membrane proteins. The results not only have potential applications in membrane protein research, but also provide insights into the structural-physical relationship of detergents.
CHEMISTRY-AN ASIAN JOURNAL
(2022)
Article
Chemistry, Medicinal
Edita Polachova, Kathrin Bach, Elena Heuten, Stancho Stanchev, Anezka Ticha, Philipp Lampe, Pavel Majer, Thomas Langer, Marius K. Lemberg, Kvido Strisovsky
Summary: The study reveals that the inhibition of PARL can activate the PINK1/Parkin pathway, promoting mitophagy in the context of Parkinson's disease. This highlights the potential of ketoamide inhibitors for cell biological studies of rhomboid proteases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Enrico Luchinat, Lucia Banci
Summary: The cellular environment plays a crucial role in the structure and function of drug targets and their interaction with potential drugs. In-cell NMR spectroscopy allows for direct studies of protein and nucleic acid structures in living cells, providing a unique approach to investigating ligand-target interactions in their native cellular context. When applied to drug screening, in-cell NMR can provide insights into binding kinetics and affinity towards cellular targets, offering a powerful tool for improving drug potency at an early stage of development.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Chuandi Yu, Wen Ding, Lei Zhu, Yuhang Zhou, Yingkui Dong, Ling Li, Juanjuan Liu, Yizhuo Wang, Zehua Li, Lina Zhu, FaJun Chen, Maosen Ruan, Dongming Qian, Yujuan Wang, Bo Wu, Huangtao Xu, Ming Li, Yunchen Bi, Hao Wang, Weiqian Wang, Peng Chao, Lei Xing, Bing Shen, Han Dai, Lisha Zha, Hongxin Zhao, Junfeng Wang
Summary: By incorporating M2(1-46) protein into nanodiscs, researchers generated vNARs that specifically bind to tetrameric M2 proteins and can block ion influx through M2 channels. This study provides a new approach for developing influenza vaccines by targeting the M2 protein.
Review
Chemistry, Multidisciplinary
Michelle D. Farrelly, Lisandra L. Martin, San H. Thang
Summary: Membrane proteins play a crucial role in cellular function and are major pharmaceutical targets. Challenges exist in the purification and study of MPs, but polymer nanodiscs have shown promise in encapsulating MPs for further analysis.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Sue Woon Tan, Negin Gooran, Hye Min Lim, Bo Kyeong Yoon, Joshua A. Jackman
Summary: In order to reduce membrane-enveloped pathogen contamination, the biological manufacturing industry is seeking alternatives to Triton X-100 (TX-100) detergent. Existing analytical approaches have limitations in studying the direct effects of lipid membrane disruption caused by TX-100 alternatives. In this study, electrochemical impedance spectroscopy (EIS) was used to investigate the membrane-disruptive behaviors of TX-100 alternatives and revealed distinct behaviors of TX-100, Simulsol, and CTAB.
Article
Chemistry, Multidisciplinary
Thirupathi Ravula, Xiaofeng Dai, Ayyalusamy Ramamoorthy
Summary: Divalent cations, especially Ca2+ and Mg2+, have a significant impact on the formation and magnetic alignment properties of polymer-based lipid nanodiscs. The interaction of these cations with lipid headgroups can promote the stacking up of nanodiscs, resulting in enhanced magnetic alignment. By optimizing the temperature and concentration of divalent metal ions, the optimal alignment of nanodiscs in the presence of an applied magnetic field can be achieved, which is crucial for various applications and structural studies using NMR.
Article
Chemistry, Multidisciplinary
Thi Kim Hoang Trinh, Andres Jorge Cabezas, Soumil Joshi, Claudio Catalano, Abu Bakkar Siddique, Weihua Qiu, Sanket Deshmukh, Amedee des Georges, Youzhong Guo
Summary: Accurate 3D structures of membrane proteins are critical, but detergents hinder their study. Researchers have developed a new class of pH-tunable membrane-active polymers, NCMNP2a-x, which can be used for high-resolution cryo-EM analysis and effectively solubilize BcTSPO. Molecular dynamic simulation provides insights into the mechanism of these polymers. NCMNP2a-x has broad applications in membrane protein research.
Article
Chemistry, Multidisciplinary
Anton P. Tyurin, Vera A. Alferova, Alexander S. Paramonov, Maxim V. Shuvalov, Gulnara K. Kudryakova, Eugene A. Rogozhin, Alexander Y. Zherebker, Vladimir A. Brylev, Alexey A. Chistov, Anna A. Baranova, Mikhail V. Biryukov, Igor A. Ivanov, Igor A. Prokhorenko, Natalia E. Grammatikova, Tatyana V. Kravchenko, Elena B. Isakova, Elena P. Mirchink, Elena G. Gladkikh, Elena V. Svirshchevskaya, Andrey V. Mardanov, Aleksey V. Beletsky, Milita V. Kocharovskaya, Valeriya V. Kulyaeva, Alexander S. Shashkov, Dmitry E. Tsvetkov, Nikolay E. Nifantiev, Alexander S. Apt, Konstantin B. Majorov, Svetlana S. Efimova, Nikolai V. Ravin, Evgeny N. Nikolaev, Olga S. Ostroumova, Genrikh S. Katrukha, Olda A. Lapchinskaya, Olga A. Dontsova, Stanislav S. Terekhov, Ilya A. Osterman, Zakhar O. Shenkarev, Vladimir A. Korshun
Summary: A novel family of natural lipoglycopeptides produced by Streptomyces sp. INA-Ac-5812, including gausemycins A and B, have been reported. These compounds exhibit pronounced activity against Gram-positive bacteria and show significant differences in mechanism compared to known glyco- and lipopeptides.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Tatyana S. Shestakova, Sergey L. Deev, Igor A. Khalymbadzha, Vladimir L. Rusinov, Alexander S. Paramonov, Alexander S. Arseniev, Zakhar O. Shenkarev, Valery N. Charushin, Oleg N. Chupakhin
Summary: The isotope-labeled antiviral drug Triazavirin containing H-2, C-13, and N-15 atoms in its structure has been synthesized, with donors including (CH3I)-C-13-H-2 and (KSCN)-C-13. The incorporation of deuterium labels and N-15 atoms was achieved using specific methods, resulting in the characterization of H-2(3),C-13(2),N-15(3)-Triazavirin through NMR spectroscopy.
CHEMISTRY OF HETEROCYCLIC COMPOUNDS
(2021)
Article
Dermatology
Mikhail A. Shulepko, Maxim L. Bychkov, Zakhar O. Shenkarev, Dmitrii S. Kulbatskii, Alexey M. Makhonin, Alexander S. Paramonov, Anton O. Chugunov, Mikhail P. Kirpichnikov, Ekaterina N. Lyukmanova
Summary: Mal de Meleda is a palmoplantar keratoderma associated with mutations in the SLURP-1 gene, which controls the growth, differentiation, and apoptosis of keratinocytes. Mutations in different regions of SLURP-1 have varying effects on its antiproliferative activity against keratinocytes. This study provides insights into the functional and structural implications of SLURP-1 mutations in the pathogenesis of Mal de Meleda.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
M. Yu. Myshkin, A. S. Paramonov, D. S. Kulbatskii, E. A. Surkova, A. A. Berkut, A. A. Vassilevski, E. N. Lyukmanova, M. P. Kirpichnikov, Z. O. Shenkarev
Summary: Voltage-gated sodium channels have modular architecture with five membrane domains, where peripheral voltage-sensing domains are responsible for channel activation and rapid inactivation. Gating modifier toxins from arthropod venoms interact with these domains, potentially serving as prototypes for new drugs. In this study, the toxin Hm-3 showed high affinity to VSD-III of human skeletal muscle Na(V)1.4 channel, with specific residues likely interacting with the channel and the lipid bilayer.
Article
Cell Biology
Dmitrii Kulbatskii, Zakhar Shenkarev, Maxim Bychkov, Eugene Loktyushov, Mikhail Shulepko, Sergey Koshelev, Igor Povarov, Alexander Popov, Steve Peigneur, Anton Chugunov, Sergey Kozlov, Irina Sharonova, Roman Efremov, Vladimir Skrebitsky, Jan Tytgat, Mikhail Kirpichnikov, Ekaterina Lyukmanova
Summary: Lypd6 is a GPI-tethered protein in the Ly-6/uPAR family that enhances Wnt/beta-catenin signaling and has been suggested to affect nicotinic acetylcholine receptors (nAChRs). The recombinant water-soluble variant of Lypd6 inhibits ACh-evoked currents at α3β4- and α7-nAChRs, and can also suppress long-term potentiation in mouse hippocampal slices. Colocalization of Lypd6 with nAChRs was observed in primary cortical and hippocampal neurons, indicating its role in cholinergic system regulation in the brain.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Alexander S. Paramonov, Ekaterina N. Lyukmanova, Alexander G. Tonevitsky, Alexander S. Arseniev, Zakhar O. Shenkarev
Summary: Thionins are small cationic cysteine-rich peptides involved in plant immune response, with Viscotoxin A3 (VtA3) from mistletoe demonstrating antimicrobial and cytotoxic activity. The structure of VtA3 in membrane-mimicking media was studied, showing stability and potential ion channel formation. VtA3 interacts with membranes and can form oligomers in certain conditions, with potential implications for membrane disruption mechanisms.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Chemistry, Organic
Sergey L. Deev, Tatyana S. Shestakova, Zakhar O. Shenkarev, Alexander S. Paramonov, Igor A. Khalymbadzha, Oleg S. Eltsov, Valery N. Charushin, Oleg N. Chupakhin
Summary: The study synthesized selectively N-15-labeled tetrazolo[1,5-b][1,2,4]-triazines and tetrazolo[1,5-a]pyrimidines, and investigated their structures and equilibrium states in solution using NMR spectroscopy. The incorporation of N-15-label(s) affected the structure and coupling constants of the compounds, providing an effective method to study tetrazole isomers and azide form.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Dmitriy Y. Ryazantsev, Mikhail Yu. Myshkin, Vera A. Alferova, Vladimir B. Tsvetkov, Elena Y. Shustova, Polina N. Kamzeeva, Polina V. Kovalets, Elvira R. Zaitseva, Nadezhda S. Baleeva, Timofei S. Zatsepin, Zakhar O. Shenkarev, Mikhail S. Baranov, Liubov I. Kozlovskaya, Andrey V. Aralov
Summary: This study investigated the potential of GFP chromophore-based compounds as anti-HIV drug candidates, identifying some promising hits that exhibited high stabilization of the LTR-III G4. The SAR analysis allowed for the identification of structural fragments important for G4 binding, and synthetic compounds developed based on this analysis showed moderate activity against HIV-I in vitro. However, this activity was accompanied by notable cytotoxicity.
Article
Biochemistry & Molecular Biology
Maxim L. Bychkov, Artem V. Kirichenko, Mikhail A. Shulepko, Irina N. Mikhaylova, Mikhail P. Kirpichnikov, Ekaterina N. Lyukmanova
Summary: Extracellular acidification promotes proliferation, migration, and invasion of metastatic melanoma cells, but has no effect on normal keratinocytes. The use of ASIC1a inhibitor mambalgin-2 can suppress these processes and induce apoptosis in melanoma cells. Targeting ASIC1a with drugs like mambalgin-2 could be a promising strategy for metastatic melanoma treatment.
Article
Chemistry, Medicinal
Alexander S. Paramonov, Mikhail A. Shulepko, Alexey M. Makhonin, Maxim L. Bychkov, Dmitrii S. Kulbatskii, Andrey M. Chernikov, Mikhail Yu Myshkin, Sergey Shabelnikov, Zakhar O. Shenkarev, Mikhail P. Kirpichnikov, Ekaterina N. Lyukmanova
Summary: In this study, we identified and analyzed the genomes of starfish A. rubens and A. planci, and predicted several proteins containing three-finger domains. One of these proteins, Lystar5, was expressed in A. rubens and negatively modulated the cholinergic system in hippocampal neurons.
Article
Biochemistry & Molecular Biology
Maxim M. M. Zaigraev, Ekaterina N. N. Lyukmanova, Alexander S. S. Paramonov, Zakhar O. O. Shenkarev, Anton O. O. Chugunov
Summary: Ly6/uPAR proteins with GPI-anchors have various positions and orientations on the membrane surface, regardless of the linker length between the LU domain and GPI-anchor. The proteins interact with the membrane through polypeptide parts and glycans. Different proteins have different contact regions with the membrane and unique orientations, indicating that GPI-anchoring does not determine the optimal pre-orientation for receptor interaction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Irina S. Panina, Sergey V. Balandin, Andrey V. Tsarev, Anton O. Chugunov, Andrey A. Tagaev, Ekaterina I. Finkina, Daria V. Antoshina, Elvira V. Sheremeteva, Alexander S. Paramonov, Jasmin Rickmeyer, Gabriele Bierbaum, Roman G. Efremov, Zakhar O. Shenkarev, Tatiana V. Ovchinnikova
Summary: To date, several lantibiotics have been found to target lipid II, a peptidoglycan precursor in bacterial cytoplasmic membrane. The alpha-component of lichenicidin, a two-component lantibiotic, contains potential lipid II binding sites. NMR spectroscopy and MD simulations provided evidence that the C-terminal domain of lichenicidin interacts with lipid II. The contact area of lipid II includes pyrophosphate, disaccharide residues, and bactoprenol's first isoprene units.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Zakhar O. Shenkarev, Yuri M. Chesnokov, Maxim M. Zaigraev, Anton O. Chugunov, Dmitrii S. Kulbatskii, Milita V. Kocharovskaya, Alexander S. Paramonov, Maxim L. Bychkov, Mikhail A. Shulepko, Dmitry E. Nolde, Roman A. Kamyshinsky, Evgeniy O. Yablokov, Alexey S. Ivanov, Mikhail P. Kirpichnikov, Ekaterina N. Lyukmanova
Summary: The alpha 7-nAChR is a potential therapeutic target for cognitive dysfunction and cancer treatment. WTX, a non-conventional neurotoxin, shows weak affinity to the alpha 7-nAChR. Our study reveals significant differences in the interaction mode between non-conventional neurotoxins and nicotinic receptors compared to classical neurotoxins, emphasizing the importance of the membrane for their interaction.
COMMUNICATIONS BIOLOGY
(2022)
