1,943 results match your criteria cys loop


Delineation of the functional properties exhibited by the Zinc-Activated Channel (ZAC) and its high-frequency ThrAla variant (rs2257020) in Xenopus oocytes.

Pharmacol Res 2021 May 4:105653. Epub 2021 May 4.

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen Ø, Denmark. Electronic address:

The signalling characteristics of the Zinc-Activated Channel (ZAC), a member of the Cys-loop receptor (CLR) superfamily, are presently poorly elucidated. The ZACN polymorphism c.454G>A encoding the ThrAla variation in ZAC is found in extremely high allele frequencies across ethnicities. Read More

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Extrasynaptic δ-subunit containing GABA receptors.

Authors:
Ayla Arslan

J Integr Neurosci 2021 Mar;20(1):173-184

School of Advanced Studies, University of Tyumen, 9 Marta Street 2k1, 625000 Tyumen, Russia.

γ-Aminobutyric acid type A receptors (GABARs) are GABA gated heteropentameric chloride channels responsible for the adult brain's primary inhibition. In specific brain cells, such as in the hippocampus, one of the subtypes of GABARs, the δ subunit containing GABARs (δ-GABARs), is predominantly expressed and located in extrasynaptic or perisynaptic positions. δ-GABARs mediate a slow constant inhibitory current called tonic inhibition. Read More

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Signal transduction through Cys-loop receptors is mediated by the nonspecific bumping of closely apposed domains.

Proc Natl Acad Sci U S A 2021 Apr;118(14)

Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801;

One of the most fundamental questions in the field of Cys-loop receptors (pentameric ligand-gated ion channels, pLGICs) is how the affinity for neurotransmitters and the conductive/nonconductive state of the transmembrane pore are correlated despite the ∼60-Å distance between the corresponding domains. Proposed mechanisms differ, but they all converge into the idea that interactions between wild-type side chains across the extracellular-transmembrane-domain (ECD-TMD) interface are crucial for this phenomenon. Indeed, the successful design of fully functional chimeras that combine intact ECD and TMD modules from different wild-type pLGICs has commonly been ascribed to the residual conservation of sequence that exists at the level of the interfacial loops even between evolutionarily distant parent channels. Read More

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Structural and Kinetic Characterization of Hyperthermophilic NADH-Dependent Persulfide Reductase from .

Archaea 2021 9;2021:8817136. Epub 2021 Mar 9.

Department of Chemistry, Pomona College, 645 N. College Ave., Claremont, CA, USA 91711.

NADH-dependent persulfide reductase (Npsr) has been proposed to facilitate dissimilatory sulfur respiration by reducing persulfide or sulfane sulfur-containing substrates to HS. The presence of this gene in the sulfate and thiosulfate-reducing DSM 4304 and other hyperthermophilic appears anomalous, as is unable to respire S and grow in the presence of elemental sulfur. To assess the role of Npsr in the sulfur metabolism of DSM 4304, the Npsr from was characterized. Read More

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Structure and gating mechanism of the α7 nicotinic acetylcholine receptor.

Cell 2021 Apr 17;184(8):2121-2134.e13. Epub 2021 Mar 17.

Department of Neuroscience, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:

The α7 nicotinic acetylcholine receptor plays critical roles in the central nervous system and in the cholinergic inflammatory pathway. This ligand-gated ion channel assembles as a homopentamer, is exceptionally permeable to Ca, and desensitizes faster than any other Cys-loop receptor. The α7 receptor has served as a prototype for the Cys-loop superfamily yet has proven refractory to structural analysis. Read More

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Role of a cysteine residue in substrate entry and catalysis in MtHIBADH: Analysis by chemical modifications and site-directed mutagenesis.

IUBMB Life 2021 Mar 16. Epub 2021 Mar 16.

Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.

Despite sharing conserved substrate-binding residues, members of 3-hydroxyisobutyrate dehydrogenase (HIBADH) superfamily show remarkable differences in substrate preference. Cysteine residues were identified within a radius of 6 Å surrounding both the active site and the substrate entry site of HIBADH enzyme from Mycobacterium tuberculosis (MtHIBADH). Chemical modification with thiol-modifying reagents, pCMB and DTNB, abrogated the dehydrogenase activity of the enzyme. Read More

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Direct Structural Insights into GABA Receptor Pharmacology.

Trends Biochem Sci 2021 Jun 3;46(6):502-517. Epub 2021 Mar 3.

Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:

GABA receptors are pentameric ligand-gated ion channels that mediate most fast neuronal inhibition in the brain. In addition to their important physiological roles, they are noteworthy in their rich pharmacology; prominent drugs used for anxiety, insomnia, and general anesthesia act through positive modulation of GABA receptors. Direct structural information for how these drugs work was absent until recently. Read More

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Sleep-related hypermotor epilepsy associated mutations uncover important kinetic roles of α4β2- nicotinic acetylcholine receptor intracellular structures.

PLoS One 2021 3;16(3):e0247825. Epub 2021 Mar 3.

Division of Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, United States of America.

Sleep-related hypermotor epilepsy (SHE) is a group of seizure disorders prominently associated with mutations in nicotinic acetylcholine receptors (nAChR). The most prevalent central nervous system nAChR subtype contains α4 and β2 subunits, in two ratios. (α4β2)2β2-nAChR have high agonist sensitivity (HS-isoform), whereas (α4β2)2α4-nAChR agonist responses exhibit a small high-sensitivity, and a predominant low-sensitivity, phase of function (LS-isoform). Read More

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Pinpoint Dual Chemical Cross-Linking Explores the Structural Dynamics of the Ubiquinone Reaction Site in Mitochondrial Complex I.

Biochemistry 2021 Mar 2;60(10):813-824. Epub 2021 Mar 2.

Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.

The ubiquinone reduction step in NADH-ubiquinone oxidoreductase (complex I) is the key to triggering proton translocation in its membrane part. Although the existence of a long and narrow quinone-access channel has been identified, it remains debatable whether the channel model can account for binding of various ligands (ubiquinones and inhibitors) to the enzyme. We previously proposed that the matrix-side interfacial region of the 49 kDa, ND1, PSST, and 39 kDa subunits, which is covered by a loop connecting transmembrane helices (TMHs) 1 and 2 of ND3, may be the area for entry of some bulky ligands into the quinone reaction cavity. Read More

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Asymmetric opening of the homopentameric 5-HT serotonin receptor in lipid bilayers.

Nat Commun 2021 02 16;12(1):1074. Epub 2021 Feb 16.

Max Planck Institute of Biophysics, Frankfurt am Main, Germany.

Pentameric ligand-gated ion channels (pLGICs) of the Cys-loop receptor family are key players in fast signal transduction throughout the nervous system. They have been shown to be modulated by the lipid environment, however the underlying mechanism is not well understood. We report three structures of the Cys-loop 5-HT serotonin receptor (5HTR) reconstituted into saposin-based lipid bilayer discs: a symmetric and an asymmetric apo state, and an asymmetric agonist-bound state. Read More

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February 2021

Mechanism of gating and partial agonist action in the glycine receptor.

Cell 2021 Feb 9;184(4):957-968.e21. Epub 2021 Feb 9.

Vollum Institute, Oregon Health & Science University, Portland, OR 97239, USA; Howard Hughes Medical Institute, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address:

Ligand-gated ion channels mediate signal transduction at chemical synapses and transition between resting, open, and desensitized states in response to neurotransmitter binding. Neurotransmitters that produce maximum open channel probabilities (Po) are full agonists, whereas those that yield lower than maximum Po are partial agonists. Cys-loop receptors are an important class of neurotransmitter receptors, yet a structure-based understanding of the mechanism of partial agonist action has proven elusive. Read More

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February 2021

Generation of cd63-deficient zebrafish to analyze the role of cd63 in viral infection.

Fish Shellfish Immunol 2021 Apr 6;111:152-159. Epub 2021 Feb 6.

Department of Marine Life Sciences & Fish Vaccine Research Center, Jeju National University, Jeju Self-Governing Province, 63243, Republic of Korea; Marine Science Institute, Jeju National University, Jeju Self-Governing Province, 63333, Republic of Korea. Electronic address:

The tetraspanin superfamily proteins are transmembrane proteins identified in a diverse range of eukaryotic organisms. Tetraspanins are involved in a variety of essential biological functions, including cell differentiation, adhesion, migration, signal transduction, intracellular trafficking, and immune responses. For an infection to occur, viruses must interact with various cell surface components, including receptors and signaling molecules. Read More

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α Subunit Histidine 55 at the Interface between Extracellular and Transmembrane Domains Affects Preactivation and Desensitization of the GABA Receptor.

ACS Chem Neurosci 2021 02 20;12(3):562-572. Epub 2021 Jan 20.

Department of Biophysics and Neuroscience, Wroclaw Medical University, Chalubinskiego 3a, Wroclaw, Dolnoślaskie 50-368, Poland.

The GABA receptor is a member of the Cys-loop family and plays a crucial role in the adult mammalian brain inhibition. Although the static structure of this receptor is emerging, the molecular mechanisms underlying its conformational transitions remain elusive. It is known that in the Cys-loop receptors, the interface between extracellular and transmembrane domains plays a key role in transmitting the "activation wave" down to the channel gate in the pore. Read More

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February 2021

Cholesterol content in the membrane promotes key lipid-protein interactions in a pentameric serotonin-gated ion channel.

Biointerphases 2021 Jan 4;15(6):061018. Epub 2021 Jan 4.

Physics Department, King's College London, Strand, London WC2R 2LS, United Kingdom.

Pentameric ligand-gated ion channels (pLGICs), embedded in the lipid membranes of nerve cells, mediate fast synaptic transmission and are major pharmaceutical targets. Because of their complexity and the limited knowledge of their structure, their working mechanisms have still to be fully unraveled at the molecular level. Over the past few years, evidence that the lipid membrane may modulate the function of membrane proteins, including pLGICs, has emerged. Read More

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January 2021

Ligand-induced transition in conformations of vicinal cysteine disulfides in proteins.

Proteins 2021 Jun 25;89(6):599-613. Epub 2021 Mar 25.

Department of Chemistry, School of Chemical Sciences, Central University of Karnataka, Kalaburagi, India.

Vicinal cysteine disulfides are thought to be associated with specific conformations of cysteine disulfides due to the restricted rotation of single bonds in an eight-membered cyclic disulfide loop. Conformations of vicinal cysteine disulfides are analyzed using χ , χ , χ , χ ', χ ' torsion angles in the crystal structures of proteins retrieved from Protein Data Bank (PDB). 85% of vicinal disulfides have (+, -)LHStaple conformation with trans configuration of the peptide bond and 9% have (-, -)RHStaple conformation with cis configured peptide bond. Read More

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Spatial Structure and Activity of Synthetic Fragments of Lynx1 and of Nicotinic Receptor Loop C Models.

Biomolecules 2020 12 22;11(1). Epub 2020 Dec 22.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.

Lynx1, membrane-bound protein co-localized with the nicotinic acetylcholine receptors (nAChRs) and regulates their function, is a three-finger protein (TFP) made of three β-structural loops, similarly to snake venom α-neurotoxin TFPs. Since the central loop II of α-neurotoxins is involved in binding to nAChRs, we have recently synthesized the fragments of Lynx1 central loop, including those with the disulfide between Cys residues introduced at N- and C-termini, some of them inhibiting muscle-type nAChR similarly to the whole-size water-soluble Lynx1 (ws-Lynx1). Literature shows that the main fragment interacting with TFPs is the C-loop of both nAChRs and acetylcholine binding proteins (AChBPs) while some ligand-binding capacity is preserved by analogs of this loop, for example, by high-affinity peptide HAP. Read More

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December 2020

Complete mitochondrial genome of Triplophysa nasobarbatula.

Mitochondrial DNA B Resour 2020 Nov 23;5(3):3771-3772. Epub 2020 Nov 23.

Guizhou Normal University, Guiyang, China.

The complete mitochondrial DNA genome of was sequenced and characterized. revealed that the complete length of its mitochondrial genome was 16,316 bp, composed of A (29.71%), C (24. Read More

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November 2020

The complete mitochondrial genome sequence and phylogenetic analysis of Sibu yak ().

Mitochondrial DNA B Resour 2019 Dec 9;5(1):46-47. Epub 2019 Dec 9.

Key Laboratory for Yak Breeding Engineering of Gansu Province, Lanzhou, PR China.

Sibu yak is famous for its excellent breed in Tibet and has become a magic way for local herdsmen to get rich. The Sibu yak, however, has been identified as an endangered bovine species. In this study, the complete mitochondrial genome of Sibu yak () was sequenced. Read More

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December 2019

The cys-loop ligand-gated ion channel gene superfamilies of the cockroaches Blattella germanica and Periplaneta americana.

Pest Manag Sci 2020 Dec 21. Epub 2020 Dec 21.

Laboratoire « Signalisation Fonctionnelle des Canaux Ioniques et Récepteurs » (SiFCIR), UPRES-EA2647 USC INRAE 1330, SFR 4207 QUASAV, UFR Sciences, Université d'Angers, Angers, France.

Background: Cockroaches are serious urban pests that can transfer disease-causing microorganisms as well as trigger allergic reactions and asthma. They are commonly managed by pesticides that act on cys-loop ligand-gated ion channels (cysLGIC). To provide further information that will enhance our understanding of how insecticides act on their molecular targets in cockroaches, we used genome and reverse transcriptase polymerase chain reaction (RT-PCR) data to characterize the cysLGIC gene superfamilies from Blattella germanica and Periplaneta americana. Read More

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December 2020

Exposure of β6/β7-Loop in Zn/Cu Superoxide Dismutase (SOD1) Is Coupled to Metal Loss and Is Transiently Reversible During Misfolding.

ACS Chem Neurosci 2021 01 16;12(1):49-62. Epub 2020 Dec 16.

Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.

Upon losing its structural integrity (misfolding), SOD1 acquires neurotoxic properties to become a pathogenic protein in ALS, a neurodegenerative disease targeting motor neurons; understanding the mechanism of misfolding may enable new treatment strategies for ALS. Here, we reported a monoclonal antibody, SE21, targeting the β6/β7-loop region of SOD1. The exposure of this region is coupled to metal loss and is entirely reversible during the early stages of misfolding. Read More

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January 2021

M4, the Outermost Helix, is Extensively Involved in Opening of the α4β2 nACh Receptor.

ACS Chem Neurosci 2021 01 9;12(1):133-139. Epub 2020 Dec 9.

Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB 1QW, United Kingdom.

Nicotinic acetylcholine receptors (nAChR) are the archetypal members of the pentameric ligand-gated ion channel (pLGIC) family, an important class of cell signaling proteins. In all members of this family, each of the five subunits has four transmembrane α-helices (M1-M4), with M2 lining the pore, then M1 and M3, and with M4 outermost and adjacent to the membrane lipids. Despite its remote location, M4 contributes both to receptor assembly and gating in pLGICs where it has been examined. Read More

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January 2021

Cyclic peptide engineered from phytocystatin inhibitory hairpin loop as an effective modulator of falcipains and potent antimalarial.

J Biomol Struct Dyn 2020 Dec 9:1-13. Epub 2020 Dec 9.

Department of Life Sciences, School of Natural Sciences, Shiv Nadar University , Uttar Pradesh , India.

Cystatins are classical competitive inhibitors of C1 family cysteine proteases (papain family). Phytocystatin superfamily shares high sequence homology and typical tertiary structure with conserved glutamine-valine-glycine (Q-X-V-X-G) loop blocking the active site of C1 proteases. Here, we develop a cysteine-bounded cyclic peptide (CYS-cIHL) and linear peptide (CYS-IHL), using the conserved inhibitory hairpin loop amino acid sequence. Read More

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December 2020

Untangling a Gordian knot: the role of a GluCl3 I321T mutation in abamectin resistance in Tetranychus urticae.

Pest Manag Sci 2021 Apr 26;77(4):1581-1593. Epub 2020 Dec 26.

Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.

Background: The cys-loop ligand-gated ion channels, including the glutamate-gated chloride channel (GluCl) and GABA-gated chloride channel (Rdl) are important targets for drugs and pesticides. The macrocyclic lactone abamectin primarily targets GluCl and is commonly used to control the spider mite Tetranychus urticae, an economically important crop pest. However, abamectin resistance has been reported for multiple T. Read More

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Heterologous production and functional characterization of copper-containing nitrite reductase and its physiological redox partner cytochrome .

Metallomics 2020 12;12(12):2084-2097

Departamento de Física, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral and CONICET, S3000ZAA Santa Fe, Argentina.

Two domain copper-nitrite reductases (NirK) contain two types of copper centers, one electron transfer (ET) center of type 1 (T1) and a catalytic site of type 2 (T2). NirK activity is pH-dependent, which has been suggested to be produced by structural modifications at high pH of some catalytically relevant residues. To characterize the pH-dependent kinetics of NirK and the relevance of T1 covalency in intraprotein ET, we studied the biochemical, electrochemical, and spectroscopic properties complemented with QM/MM calculations of Bradyrhizobium japonicum NirK (BjNirK) and of its electron donor cytochrome c550 (BjCycA). Read More

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December 2020

Proline Residues Contribute to Efficient GABA Receptor Function.

ACS Chem Neurosci 2020 12 17;11(24):4215-4222. Epub 2020 Nov 17.

Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, United Kingdom.

GABA receptors are homomeric pentameric ligand-gated ion channels (pLGICs) and are useful for probing the molecular details of the mechanism of action in this important protein family. Here, we explore the role of proline (Pro) residues by creating mutant receptors, expressing them in HEK293 cells, and using fluorescent membrane potential sensitive dye to monitor receptor activity. The data revealed that 3 of the Pro-to-alanine substitutions resulted in nonfunctional receptors (one in the Cys-loop, one in loop A and one in the β2-β3 loop), 7 resulted in increased EC values, and the remaining 13 resulted in receptors with properties similar to WT receptors. Read More

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December 2020

Structure analysis of thymidylate synthase from white spot syndrome virus reveals WSSV-specific structural elements.

Int J Biol Macromol 2021 Jan 14;167:1168-1175. Epub 2020 Nov 14.

Institute of Life Sciences, Bhubaneswar 751023, Odisha, India. Electronic address:

White spot syndrome virus (WSSV), the causative agent of white spot disease (WSD) severely affecting crustacean life forms, is highly contagious and forms the principal cause of massive economic losses in the shrimp aquaculture industry. Previous studies have demonstrated thymidylate synthase as a successful anti-cancer therapeutic drug target, leading to various anti-cancer drugs. The differential utilization of nucleotide precursors between white spot syndrome virus and shrimp encouraged us to analyze WSSV-thymidylate synthase (wTS). Read More

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January 2021

Bacterial OTU deubiquitinases regulate substrate ubiquitination upon Legionella infection.

Elife 2020 11 13;9. Epub 2020 Nov 13.

Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany.

causes a severe pneumonia known as Legionnaires' disease. During the infection, Legionella injects more than 300 effector proteins into host cells. Among them are enzymes involved in altering the host-ubiquitination system. Read More

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November 2020

Change the channel: CysLoop receptor antagonists from nature.

Pest Manag Sci 2020 Nov 1. Epub 2020 Nov 1.

Department of Chemistry, Scripps Research, La Jolla, CA, USA.

Vertebrate and invertebrate ligand-gated ion channels (LGICs) exhibit significant structural homology and often share ligands. As a result, ligands with activity against one class can be brought to bear against another, including for development as insecticides. Receptor selectivity, metabolism and distribution must then be optimized using chemical synthesis. Read More

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November 2020

Editorial: From Peptide and Protein Toxins to Ion Channel Structure/Function and Drug Design.

Front Pharmacol 2020 25;11:548366. Epub 2020 Sep 25.

Department of Molecular Neuroimmune Signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.

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September 2020

Structural Insights into the Active Site Formation of DUSP22 in N-loop-containing Protein Tyrosine Phosphatases.

Int J Mol Sci 2020 Oct 12;21(20). Epub 2020 Oct 12.

Institute of Bioinformatics and Structural Biology, Department of Life Science, National Tsing Hua University, Hsinchu 30013, Taiwan.

Cysteine-based protein tyrosine phosphatases (Cys-based PTPs) perform dephosphorylation to regulate signaling pathways in cellular responses. The hydrogen bonding network in their active site plays an important conformational role and supports the phosphatase activity. Nearly half of dual-specificity phosphatases (DUSPs) use three conserved residues, including aspartate in the D-loop, serine in the P-loop, and asparagine in the N-loop, to form the hydrogen bonding network, the D-, P-, N-triloop interaction (DPN-triloop interaction). Read More

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October 2020