Article
Biochemistry & Molecular Biology
Kirsten L. Mcmahon, Henrik O'Brien, Christina I. Schroeder, Jennifer R. Deuis, Dhananjeyan Venkatachalam, Di Huang, Brad R. Green, Pradip K. Bandyopadhyay, Qing Li, Mark Yandell, Helena Safavi-Hemami, Baldomero M. Olivera, Irina Vetter, Samuel D. Robinson
Summary: This study identified new mu-conotoxins from species of the subgenera Textilia and Afonsoconus and investigated their selectivity at human Na-V channels using RNA-seq and DNA analysis techniques.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Chemistry, Medicinal
James R. Groome
Summary: This article reviews the study of marine toxins, particularly on their actions on sodium ion channels regulated by transmembrane voltage and neurotransmitters. The focus is on the diverse conotoxin peptides and their potential applications in evolutionary relationships, biological actions, disease therapy, and understanding the structure of ion channels at the atomic level.
Article
Chemistry, Multidisciplinary
Huilei Dong, Jinjing Li, Hongtan Liu, Shuaimin Lu, Junjie Wu, Youming Zhang, Yizhen Yin, Yibing Zhao, Chuanliu Wu
Summary: This study presents a new method for discovering de novo DRPs with new structures and functions not derived from natural peptides by designing and synthesizing noncanonical bisthiol motifs. The method enables the in vitro expression of bicyclic peptides with two noncanonical and orthogonal disulfide bonds and the selection of new peptide ligands with nanomolar affinity to proteins using a mRNA-encoded bicyclic peptide library.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Abdelfattah Faouzi, Haoqing Wang, Saheem A. Zaidi, Jeffrey F. DiBerto, Tao Che, Qianhui Qu, Michael J. Robertson, Manish K. Madasu, Amal El Daibani, Balazs R. Varga, Tiffany Zhang, Claudia Ruiz, Shan Liu, Jin Xu, Kevin Appourchaux, Samuel T. Slocum, Shainnel O. Eans, Michael D. Cameron, Ream Al-Hasani, Ying Xian Pan, Bryan L. Roth, Jay P. McLaughlin, Georgios Skiniotis, Vsevolod Katritch, Brian K. Kobilka, Susruta Majumdar
Summary: This study presents an approach to design safer analgesics by targeting a conserved sodium ion-binding site in mu-opioid receptor (mu OR) using bitopic fentanyl derivatives. Cryo-electron microscopy structures reveal key interactions between the ligands and mu OR, demonstrating nanomolar potency, high efficacy, and reduced adverse effects. This study suggests the potential of the mu OR sodium ion-binding site as a target for the design of safer analgesics.
Article
Biochemical Research Methods
Lina Zhao, Lisa M. Barber, Andrew Hung
Summary: Conotoxins are a family of neurotoxic peptides, with MfVIA being one of them, exhibiting ideal selectivity inhibition on NaV1.8. Molecular dynamics simulations were used to study the effects of various mutations on the structure and dynamics of MfVIA at key residues.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2021)
Article
Multidisciplinary Sciences
Quynh N. Vo, Paween Mahinthichaichan, Jana Shen, Christopher R. Ellis
Summary: This research elucidates the detailed binding mechanism of fentanyl in mOR, identifying a secondary binding mode that is only accessible when His297 is in a neutral HID tautomer state.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Li-Shen Soh, G. Veera Singham
Summary: This study investigates the influence of host microbiota on the susceptibility of bed bugs to different insecticides and suggests that bacterial symbionts may play a role in modulating insecticide susceptibility in bed bugs.
SCIENTIFIC REPORTS
(2022)
Review
Dermatology
Pengfei Sun, Zhonglei Ji, Zhengyong Li, Bo Pan
Summary: This study explored the use of BTX-A and conotoxin in preventing skin scar hyperplasia, analyzing their advantages and disadvantages, and providing a perspective on the application of conotoxin in scar prevention.
JOURNAL OF COSMETIC DERMATOLOGY
(2021)
Article
Cell Biology
Yun Wu, Manyi Yang, Yubin Li, Wei Zhang, Maojun Zhou
Summary: Conotoxin Lt7b, a novel O-2-superfamily conotoxin, was synthesized and evaluated in this study. It was found that Lt7b could inhibit calcium currents, increase sodium currents, and had no obvious effects on potassium currents. Patch clamp experiments on ion channel subtypes showed that Lt7b could selectively inhibit certain types of currents. Furthermore, Lt7b exhibited no apparent toxicity to cells and increased the pain threshold in mice.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Neurosciences
Jie Xu, Yan-Tian Lv, Xiao-Yun Zhao, Jing-Jing Wang, Zhong-Shan Shen, Jian Li, Fei-Fei Zhang, Jing Liu, Xiao-Hui Wang, Yun Xu, Qi Geng, Yi-Tong Ding, Jing-Jing Xu, Meng-Jiao Tan, Zhi-Xiao Li, Ran Wang, Jian Chen, Wen Sun, Meng Cui, Diomedes E. Logothetis, Jun-li Cao, Qiong-Yao Tang, Zhe Zhang
Summary: In this study, two potential sodium-sensitive sites were identified in the C-terminal domain of the rat Slack channel, and R379 was determined to be a chloride interaction site. These findings contribute to a better understanding of the sodium gating mechanism and the regulation of Slack channel function.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Pharmacology & Pharmacy
Ian H. H. Kimball, Phuong T. T. Nguyen, Baldomero M. M. Olivera, Jon T. T. Sack, Vladimir Yarov-Yarovoy
Summary: In this study, the interactions between mu-Conotoxin KIIIA and the human Na(V)1.7 channel were investigated using Rosetta computational modeling and in silico docking. The specific pairwise contacts between KIIIA and hNa(V)1.7 were predicted using RosettaDock and experimentally validated. Comparison with the cryo-EM structure of KIIIA-hNa(V)1.2 revealed important similarities and differences between Na-V channel subtypes, which may have implications for understanding the molecular mechanism of toxin block. The integrative approach used in this study suggests that Rosetta structural predictions can be useful for designing biologics targeting specific Na-V channels.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Physical
Mario Gonzalez-Jimenez, Gopakumar Ramakrishnan, Nikita V. Tukachev, Hans M. Senn, Klaas Wynne
Summary: Research indicates that low-frequency vibrations of G-quadruplexes may have an impact on the biological function of DNA, and G-quadruplexes exhibit modes at a higher frequency than B-DNA, suggesting that changes in molecular stiffness alter its vibrational profile.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Xuehui Guo, Yiming Jiang, Daiqian Xie, Yanzi Zhou
Summary: Poly(ethylene terephthalate) (PET) is widely used in daily life, but its non-degradability causes environmental and health problems. PETase from Ideonella sakaiensis has shown the highest PET degradation activity, but the crystal structure of the PET-PETase complex remains unknown. Molecular docking and dynamics simulations were used to study the binding and interactions between PET and PETase. The PET oligomers adopt stable conformations in a shallow cleft on PETase, with only four moieties fitting in the binding cleft. This study provides insights into PET binding and can aid the design of more efficient PETase variants for plastic degradation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Engineering, Electrical & Electronic
Seong Ki Yoo, Nidhi Simmons, Simon L. Cotton, Paschalis C. Sofotasios, Michail Matthaiou, Mikko Valkama, George K. Karagiannidis
Summary: The paper presents and extensively investigates the kappa-mu / inverse gamma and eta-mu / inverse gamma composite fading models, deriving closed-form expressions for fundamental statistics and performance analysis. Extensive field measurements demonstrate the suitability and accuracy of the new models for characterizing composite fading channels.
IEEE TRANSACTIONS ON COMMUNICATIONS
(2021)
Article
Neurosciences
Daniel Szollosi, Thomas Stockner
Summary: The serotonin transporter (SERT) plays a crucial role in terminating neurotransmission and its altered function is linked to various neurological diseases. Through molecular dynamics simulations, researchers identified a well-defined pathway for sodium entry into SERT, shedding light on the initial step of the serotonin transport cycle. The induced-fit mechanism accompanying sodium binding leads to new conformations and reduced local dynamics, providing insights into the transport process.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)