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Seok-Yong Lee

George Barth Geller Distinguished Professor of Molecular Biology
Biochemistry
Duke Box 3711, Sands 269, Durham, NC 27710
269 Sands, 303 Research Dr, Durham, NC 27710

Selected Publications


Structural insights into the FtsEX-EnvC complex regulation on septal peptidoglycan hydrolysis in Vibrio cholerae.

Journal Article Structure · February 1, 2024 During bacterial cell division, hydrolysis of septal peptidoglycan (sPG) is crucial for cell separation. This sPG hydrolysis is performed by the enzyme amidases whose activity is regulated by the integral membrane protein complex FtsEX-EnvC. FtsEX is an AT ... Full text Link to item Cite

Antiviral drug recognition and elevator-type transport motions of CNT3

Journal Article Nature Chemical Biology · January 1, 2024 Nucleoside analogs have broad clinical utility as antiviral drugs. Key to their systemic distribution and cellular entry are human nucleoside transporters. Here, we establish that the human concentrative nucleoside transporter 3 (CNT3) interacts with antiv ... Full text Cite

Molecular basis of polyspecific drug and xenobiotic recognition by OCT1 and OCT2.

Journal Article Nat Struct Mol Biol · July 2023 A wide range of endogenous and xenobiotic organic ions require facilitated transport systems to cross the plasma membrane for their disposition. In mammals, organic cation transporter (OCT) subtypes 1 and 2 (OCT1 and OCT2, also known as SLC22A1 and SLC22A2 ... Full text Link to item Cite

TRPV4-Rho GTPase complex structures reveal mechanisms of gating and disease.

Journal Article Nat Commun · June 23, 2023 Crosstalk between ion channels and small GTPases is critical during homeostasis and disease, but little is known about the structural underpinnings of these interactions. TRPV4 is a polymodal, calcium-permeable cation channel that has emerged as a potentia ... Full text Link to item Cite

Synthesis of macrocyclic nucleoside antibacterials and their interactions with MraY.

Journal Article Nat Commun · December 20, 2022 The development of new antibacterial drugs with different mechanisms of action is urgently needed to address antimicrobial resistance. MraY is an essential membrane enzyme required for bacterial cell wall synthesis. Sphaerimicins are naturally occurring ma ... Full text Link to item Cite

Activation mechanism of the mouse cold-sensing TRPM8 channel by cooling agonist and PIP2.

Journal Article Science · October 14, 2022 The transient receptor potential melastatin 8 (TRPM8) channel is the primary molecular transducer responsible for the cool sensation elicited by menthol and cold in mammals. TRPM8 activation is controlled by cooling compounds together with the membrane lip ... Full text Link to item Cite

Methotrexate recognition by the human reduced folate carrier SLC19A1.

Journal Article Nature · September 2022 Folates are essential nutrients with important roles as cofactors in one-carbon transfer reactions, being heavily utilized in the synthesis of nucleic acids and the metabolism of amino acids during cell division1,2. Mammals lack de novo folate synthesis pa ... Full text Link to item Cite

Structural basis for inhibition and regulation of a chitin synthase from Candida albicans.

Journal Article Nat Struct Mol Biol · July 2022 Chitin is an essential component of the fungal cell wall. Chitin synthases (Chss) catalyze chitin formation and translocation across the membrane and are targets of antifungal agents, including nikkomycin Z and polyoxin D. Lack of structural insights into ... Full text Link to item Cite

Structure and Mechanism of the Lipid Flippase MurJ.

Journal Article Annu Rev Biochem · June 21, 2022 Biosynthesis of many important polysaccharides (including peptidoglycan, lipopolysaccharide, and N-linked glycans) necessitates the transport of lipid-linked oligosaccharides (LLO) across membranes from their cytosolic site of synthesis to their sites of u ... Full text Link to item Cite

Recent advances on the inhibition of human solute carriers: Therapeutic implications and mechanistic insights.

Journal Article Curr Opin Struct Biol · June 2022 Solute carriers (SLCs) are membrane transport proteins tasked with mediating passage of hydrophilic molecules across lipid bilayers. Despite the extensive roles played in all aspects of human biology, SLCs remain vastly under-explored as therapeutic target ... Full text Link to item Cite

Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis.

Journal Article Nat Commun · May 24, 2022 Single particle cryo-EM often yields multiple protein conformations within a single dataset, but experimentally deducing the temporal relationship of these conformers within a conformational trajectory is not trivial. Here, we use thermal titration methods ... Full text Link to item Cite

Heat-dependent opening of TRPV1 in the presence of capsaicin.

Journal Article Nature structural & molecular biology · July 2021 Transient receptor potential vanilloid member 1 (TRPV1) is a Ca2+-permeable cation channel that serves as the primary heat and capsaicin sensor in humans. Using cryo-EM, we have determined the structures of apo and capsaicin-bound full-length ra ... Full text Cite

Toward a Molecular Basis of Cellular Nucleoside Transport in Humans.

Journal Article Chem Rev · May 12, 2021 Nucleosides play central roles in all facets of life, from metabolism to cellular signaling. Because of their physiochemical properties, nucleosides are lipid bilayer impermeable and thus rely on dedicated transport systems to cross biological membranes. I ... Full text Link to item Cite

Synthesis and evaluation of cyclopentane-based muraymycin analogs targeting MraY.

Journal Article Eur J Med Chem · April 5, 2021 Antibiotic resistance is one of the most challenging global health issues and presents an urgent need for the development of new antibiotics. In this regard, phospho-MurNAc-pentapeptide translocase (MraY), an essential enzyme in the early stages of peptido ... Full text Link to item Cite

Sample preparation of the human TRPA1 ion channel for cryo-EM studies.

Chapter · 2021 The transient receptor potential ankyrin 1 (TRPA1) ion channel is a member of the TRP channel family that is involved in sensing noxious stimuli that elicit pain and inflammation. Because of its critical physiological role and therapeutic importance, great ... Full text Link to item Cite

Current View of Ligand and Lipid Recognition by the Menthol Receptor TRPM8.

Journal Article Trends Biochem Sci · September 2020 Transient receptor potential (TRP) melastatin member 8 (TRPM8), which is a calcium-permeable ion channel, functions as the primary molecular sensor of cold and menthol in humans. Recent cryoelectron microscopy (cryo-EM) studies of TRPM8 have shown distinct ... Full text Link to item Cite

Structures of Bacterial MraY and Human GPT Provide Insights into Rational Antibiotic Design.

Journal Article J Mol Biol · August 21, 2020 The widespread emergence of antibiotic resistance in pathogens necessitates the development of antibacterial agents inhibiting underexplored targets in bacterial metabolism. One such target is phospho-MurNAc-pentapeptide translocase (MraY), an essential in ... Full text Link to item Cite

Structural Insights into Electrophile Irritant Sensing by the Human TRPA1 Channel.

Journal Article Neuron · March 4, 2020 Transient receptor potential channel subfamily A member 1 (TRPA1) is a Ca2+-permeable cation channel that serves as one of the primary sensors of environmental irritants and noxious substances. Many TRPA1 agonists are electrophiles that are recognized by T ... Full text Link to item Cite

The role of π-helices in TRP channel gating.

Journal Article Curr Opin Struct Biol · October 2019 Transient Receptor Potential (TRP) channels are a large superfamily of polymodal ion channels, which perform important roles in numerous physiological processes. The architecture of their transmembrane (TM) domains closely resembles that of voltage-gated p ... Full text Link to item Cite

Structural insights into the FtsEX-EnvC complex regulation on septal peptidoglycan hydrolysis in Vibrio cholerae.

Journal Article Structure · February 1, 2024 During bacterial cell division, hydrolysis of septal peptidoglycan (sPG) is crucial for cell separation. This sPG hydrolysis is performed by the enzyme amidases whose activity is regulated by the integral membrane protein complex FtsEX-EnvC. FtsEX is an AT ... Full text Link to item Cite

Antiviral drug recognition and elevator-type transport motions of CNT3

Journal Article Nature Chemical Biology · January 1, 2024 Nucleoside analogs have broad clinical utility as antiviral drugs. Key to their systemic distribution and cellular entry are human nucleoside transporters. Here, we establish that the human concentrative nucleoside transporter 3 (CNT3) interacts with antiv ... Full text Cite

Molecular basis of polyspecific drug and xenobiotic recognition by OCT1 and OCT2.

Journal Article Nat Struct Mol Biol · July 2023 A wide range of endogenous and xenobiotic organic ions require facilitated transport systems to cross the plasma membrane for their disposition. In mammals, organic cation transporter (OCT) subtypes 1 and 2 (OCT1 and OCT2, also known as SLC22A1 and SLC22A2 ... Full text Link to item Cite

TRPV4-Rho GTPase complex structures reveal mechanisms of gating and disease.

Journal Article Nat Commun · June 23, 2023 Crosstalk between ion channels and small GTPases is critical during homeostasis and disease, but little is known about the structural underpinnings of these interactions. TRPV4 is a polymodal, calcium-permeable cation channel that has emerged as a potentia ... Full text Link to item Cite

Synthesis of macrocyclic nucleoside antibacterials and their interactions with MraY.

Journal Article Nat Commun · December 20, 2022 The development of new antibacterial drugs with different mechanisms of action is urgently needed to address antimicrobial resistance. MraY is an essential membrane enzyme required for bacterial cell wall synthesis. Sphaerimicins are naturally occurring ma ... Full text Link to item Cite

Activation mechanism of the mouse cold-sensing TRPM8 channel by cooling agonist and PIP2.

Journal Article Science · October 14, 2022 The transient receptor potential melastatin 8 (TRPM8) channel is the primary molecular transducer responsible for the cool sensation elicited by menthol and cold in mammals. TRPM8 activation is controlled by cooling compounds together with the membrane lip ... Full text Link to item Cite

Methotrexate recognition by the human reduced folate carrier SLC19A1.

Journal Article Nature · September 2022 Folates are essential nutrients with important roles as cofactors in one-carbon transfer reactions, being heavily utilized in the synthesis of nucleic acids and the metabolism of amino acids during cell division1,2. Mammals lack de novo folate synthesis pa ... Full text Link to item Cite

Structural basis for inhibition and regulation of a chitin synthase from Candida albicans.

Journal Article Nat Struct Mol Biol · July 2022 Chitin is an essential component of the fungal cell wall. Chitin synthases (Chss) catalyze chitin formation and translocation across the membrane and are targets of antifungal agents, including nikkomycin Z and polyoxin D. Lack of structural insights into ... Full text Link to item Cite

Structure and Mechanism of the Lipid Flippase MurJ.

Journal Article Annu Rev Biochem · June 21, 2022 Biosynthesis of many important polysaccharides (including peptidoglycan, lipopolysaccharide, and N-linked glycans) necessitates the transport of lipid-linked oligosaccharides (LLO) across membranes from their cytosolic site of synthesis to their sites of u ... Full text Link to item Cite

Recent advances on the inhibition of human solute carriers: Therapeutic implications and mechanistic insights.

Journal Article Curr Opin Struct Biol · June 2022 Solute carriers (SLCs) are membrane transport proteins tasked with mediating passage of hydrophilic molecules across lipid bilayers. Despite the extensive roles played in all aspects of human biology, SLCs remain vastly under-explored as therapeutic target ... Full text Link to item Cite

Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis.

Journal Article Nat Commun · May 24, 2022 Single particle cryo-EM often yields multiple protein conformations within a single dataset, but experimentally deducing the temporal relationship of these conformers within a conformational trajectory is not trivial. Here, we use thermal titration methods ... Full text Link to item Cite

Heat-dependent opening of TRPV1 in the presence of capsaicin.

Journal Article Nature structural & molecular biology · July 2021 Transient receptor potential vanilloid member 1 (TRPV1) is a Ca2+-permeable cation channel that serves as the primary heat and capsaicin sensor in humans. Using cryo-EM, we have determined the structures of apo and capsaicin-bound full-length ra ... Full text Cite

Toward a Molecular Basis of Cellular Nucleoside Transport in Humans.

Journal Article Chem Rev · May 12, 2021 Nucleosides play central roles in all facets of life, from metabolism to cellular signaling. Because of their physiochemical properties, nucleosides are lipid bilayer impermeable and thus rely on dedicated transport systems to cross biological membranes. I ... Full text Link to item Cite

Synthesis and evaluation of cyclopentane-based muraymycin analogs targeting MraY.

Journal Article Eur J Med Chem · April 5, 2021 Antibiotic resistance is one of the most challenging global health issues and presents an urgent need for the development of new antibiotics. In this regard, phospho-MurNAc-pentapeptide translocase (MraY), an essential enzyme in the early stages of peptido ... Full text Link to item Cite

Sample preparation of the human TRPA1 ion channel for cryo-EM studies.

Chapter · 2021 The transient receptor potential ankyrin 1 (TRPA1) ion channel is a member of the TRP channel family that is involved in sensing noxious stimuli that elicit pain and inflammation. Because of its critical physiological role and therapeutic importance, great ... Full text Link to item Cite

Current View of Ligand and Lipid Recognition by the Menthol Receptor TRPM8.

Journal Article Trends Biochem Sci · September 2020 Transient receptor potential (TRP) melastatin member 8 (TRPM8), which is a calcium-permeable ion channel, functions as the primary molecular sensor of cold and menthol in humans. Recent cryoelectron microscopy (cryo-EM) studies of TRPM8 have shown distinct ... Full text Link to item Cite

Structures of Bacterial MraY and Human GPT Provide Insights into Rational Antibiotic Design.

Journal Article J Mol Biol · August 21, 2020 The widespread emergence of antibiotic resistance in pathogens necessitates the development of antibacterial agents inhibiting underexplored targets in bacterial metabolism. One such target is phospho-MurNAc-pentapeptide translocase (MraY), an essential in ... Full text Link to item Cite

Structural Insights into Electrophile Irritant Sensing by the Human TRPA1 Channel.

Journal Article Neuron · March 4, 2020 Transient receptor potential channel subfamily A member 1 (TRPA1) is a Ca2+-permeable cation channel that serves as one of the primary sensors of environmental irritants and noxious substances. Many TRPA1 agonists are electrophiles that are recognized by T ... Full text Link to item Cite

The role of π-helices in TRP channel gating.

Journal Article Curr Opin Struct Biol · October 2019 Transient Receptor Potential (TRP) channels are a large superfamily of polymodal ion channels, which perform important roles in numerous physiological processes. The architecture of their transmembrane (TM) domains closely resembles that of voltage-gated p ... Full text Link to item Cite

Visualizing structural transitions of ligand-dependent gating of the TRPM2 channel.

Journal Article Nat Commun · August 20, 2019 The transient receptor potential melastatin 2 (TRPM2) channel plays a key role in redox sensation in many cell types. Channel activation requires binding of both ADP-ribose (ADPR) and Ca2+. The recently published TRPM2 structures from Danio rerio in the li ... Full text Link to item Cite

Chemical logic of MraY inhibition by antibacterial nucleoside natural products.

Journal Article Nat Commun · July 2, 2019 Novel antibacterial agents are needed to address the emergence of global antibiotic resistance. MraY is a promising candidate for antibiotic development because it is the target of five classes of naturally occurring nucleoside inhibitors with potent antib ... Full text Link to item Cite

Structures of human ENT1 in complex with adenosine reuptake inhibitors.

Journal Article Nat Struct Mol Biol · July 2019 The human equilibrative nucleoside transporter 1 (hENT1), a member of the SLC29 family, plays crucial roles in adenosine signaling, cellular uptake of nucleoside for DNA and RNA synthesis, and nucleoside-derived anticancer and antiviral drug transport in h ... Full text Link to item Cite

Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes.

Journal Article Elife · May 15, 2019 The Transient Receptor Potential Vanilloid 2 (TRPV2) channel is a member of the temperature-sensing thermoTRPV family. Recent advances in cryo-electronmicroscopy (cryo-EM) and X-ray crystallography have provided many important insights into the gating mech ... Full text Open Access Link to item Cite

Regulatory switch at the cytoplasmic interface controls TRPV channel gating.

Journal Article Elife · May 9, 2019 Temperature-sensitive transient receptor potential vanilloid (thermoTRPV) channels are activated by ligands and heat, and are involved in various physiological processes. ThermoTRPV channels possess a large cytoplasmic ring consisting of N-terminal ankyrin ... Full text Open Access Link to item Cite

Visualizing conformation transitions of the Lipid II flippase MurJ.

Journal Article Nat Commun · April 15, 2019 The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases. MurJ is the flippase for the lipi ... Full text Link to item Cite

Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel.

Journal Article Science · March 1, 2019 Transient receptor potential melastatin member 8 (TRPM8) is a calcium ion (Ca2+)-permeable cation channel that serves as the primary cold and menthol sensor in humans. Activation of TRPM8 by cooling compounds relies on allosteric actions of agonist and mem ... Full text Link to item Cite

Conformational ensemble of the human TRPV3 ion channel.

Journal Article Nat Commun · November 14, 2018 Transient receptor potential vanilloid channel 3 (TRPV3), a member of the thermosensitive TRP (thermoTRPV) channels, is activated by warm temperatures and serves as a key regulator of normal skin physiology through the release of pro-inflammatory messenger ... Full text Link to item Cite

Cryo-EM structure of a mitochondrial calcium uniporter.

Journal Article Science · August 3, 2018 Calcium transport plays an important role in regulating mitochondrial physiology and pathophysiology. The mitochondrial calcium uniporter (MCU) is a calcium-selective ion channel that is the primary mediator for calcium uptake into the mitochondrial matrix ... Full text Link to item Cite

Conformational plasticity in the selectivity filter of the TRPV2 ion channel.

Journal Article Nat Struct Mol Biol · May 2018 Transient receptor potential vanilloid (TRPV) channels are activated by ligands and heat and are involved in various physiological processes. In contrast to the architecturally related voltage-gated cation channels, TRPV1 and TRPV2 subtypes possess another ... Full text Link to item Cite

GlcNAc-1-P-transferase-tunicamycin complex structure reveals basis for inhibition of N-glycosylation.

Journal Article Nat Struct Mol Biol · March 2018 N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders. The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase ... Full text Link to item Cite

Expression and Role of Voltage-Gated Sodium Channels in Human Dorsal Root Ganglion Neurons with Special Focus on Nav1.7, Species Differences, and Regulation by Paclitaxel.

Journal Article Neurosci Bull · February 2018 Voltage-gated sodium channels (Navs) play an important role in human pain sensation. However, the expression and role of Nav subtypes in native human sensory neurons are unclear. To address this issue, we obtained human dorsal root ganglion (hDRG) tissues ... Full text Link to item Cite

Differential Inhibition of Nav1.7 and Neuropathic Pain by Hybridoma-Produced and Recombinant Monoclonal Antibodies that Target Nav1.7 : Differential activities of Nav1.7-targeting monoclonal antibodies.

Journal Article Neurosci Bull · February 2018 The voltage-gated Na+ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na+ currents and pain and itch responses in mice. Here, we investigated whet ... Full text Link to item Cite

Structure of the cold- and menthol-sensing ion channel TRPM8.

Journal Article Science · January 12, 2018 Transient receptor potential melastatin (TRPM) cation channels are polymodal sensors that are involved in a variety of physiological processes. Within the TRPM family, member 8 (TRPM8) is the primary cold and menthol sensor in humans. We determined the cry ... Full text Open Access Link to item Cite

Cryo-electron microscopy structure of the lysosomal calcium-permeable channel TRPML3.

Journal Article Nature · October 19, 2017 The modulation of ion channel activity by lipids is increasingly recognized as a fundamental component of cellular signalling. The transient receptor potential mucolipin (TRPML) channel family belongs to the TRP superfamily and is composed of three members ... Full text Link to item Cite

Visualizing multistep elevator-like transitions of a nucleoside transporter.

Journal Article Nature · May 4, 2017 Membrane transporters move substrates across the membrane by alternating access of their binding sites between the opposite sides of the membrane. An emerging model of this process is the elevator mechanism, in which a substrate-binding transport domain mo ... Full text Link to item Cite

Crystal structure of the MOP flippase MurJ in an inward-facing conformation.

Journal Article Nat Struct Mol Biol · February 2017 Peptidoglycan (PG) protects bacteria from osmotic lysis, and its biogenesis is a key antibiotic target. A central step in PG biosynthesis is flipping of the lipid-linked PG precursor lipid II across the cytoplasmic membrane for subsequent incorporation int ... Full text Link to item Cite

Current view on regulation of voltage-gated sodium channels by calcium and auxiliary proteins.

Journal Article Protein Sci · September 2016 In cardiac and skeletal myocytes, and in most neurons, the opening of voltage-gated Na(+) channels (NaV channels) triggers action potentials, a process that is regulated via the interactions of the channels' intercellular C-termini with auxiliary proteins ... Full text Link to item Cite

Structural insights into inhibition of lipid I production in bacterial cell wall synthesis.

Journal Article Nature · May 26, 2016 Antibiotic-resistant bacterial infection is a serious threat to public health. Peptidoglycan biosynthesis is a well-established target for antibiotic development. MraY (phospho-MurNAc-pentapeptide translocase) catalyses the first and an essential membrane ... Full text Link to item Cite

Cryo-electron microscopy structure of the TRPV2 ion channel.

Journal Article Nat Struct Mol Biol · February 2016 Transient receptor potential vanilloid (TRPV) cation channels are polymodal sensors involved in a variety of physiological processes. TRPV2, a member of the TRPV family, is regulated by temperature, by ligands, such as probenecid and cannabinoids, and by l ... Full text Link to item Cite

Liposome reconstitution and transport assay for recombinant transporters.

Journal Article Methods Enzymol · 2015 Secondary active transporters are responsible for the cellular uptake of many biologically important molecules, including neurotransmitters, nutrients, and drugs. Because of their physiological and clinical importance, a method for assessing their transpor ... Full text Link to item Cite

Structural analyses of Ca²⁺/CaM interaction with NaV channel C-termini reveal mechanisms of calcium-dependent regulation.

Journal Article Nat Commun · September 18, 2014 Ca(2+) regulates voltage-gated Na(+) (NaV) channels, and perturbed Ca(2+) regulation of NaV function is associated with epilepsy syndromes, autism and cardiac arrhythmias. Understanding the disease mechanisms, however, has been hindered by a lack of struct ... Full text Link to item Cite

Structural basis of nucleoside and nucleoside drug selectivity by concentrative nucleoside transporters.

Journal Article Elife · July 31, 2014 Concentrative nucleoside transporters (CNTs) are responsible for cellular entry of nucleosides, which serve as precursors to nucleic acids and act as signaling molecules. CNTs also play a crucial role in the uptake of nucleoside-derived drugs, including an ... Full text Link to item Cite

A monoclonal antibody that targets a NaV1.7 channel voltage sensor for pain and itch relief.

Journal Article Cell · June 5, 2014 Voltage-gated sodium (NaV) channels control the upstroke of the action potentials in excitable cells. Multiple studies have shown distinct roles of NaV channel subtypes in human physiology and diseases, but subtype-specific therapeutics are lacking and the ... Full text Link to item Cite

Crystal structure of MraY, an essential membrane enzyme for bacterial cell wall synthesis.

Journal Article Science · August 30, 2013 MraY (phospho-MurNAc-pentapeptide translocase) is an integral membrane enzyme that catalyzes an essential step of bacterial cell wall biosynthesis: the transfer of the peptidoglycan precursor phospho-MurNAc-pentapeptide to the lipid carrier undecaprenyl ph ... Full text Link to item Cite

Crystal structure of MraY, an essential membrane enzyme for bacterial cell wall synthesis

Journal Article Science · 2013 MraY (phospho-MurNAc-pentapeptide translocase) is an integral membrane enzyme that catalyzes an essential step of bacterial cell wall biosynthesis: the transfer of the peptidoglycan precursor phospho-MurNAc-pentapeptide to the lipid carrier undecaprenyl ph ... Full text Cite

Crystal structure of the ternary complex of a NaV C-terminal domain, a fibroblast growth factor homologous factor, and calmodulin.

Journal Article Structure · July 3, 2012 Voltage-gated Na⁺ (Na(V)) channels initiate neuronal action potentials. Na(V) channels are composed of a transmembrane domain responsible for voltage-dependent Na⁺ conduction and a cytosolic C-terminal domain (CTD) that regulates channel function through i ... Full text Link to item Cite

Crystal structure of a concentrative nucleoside transporter from Vibrio cholerae at 2.4 Å.

Journal Article Nature · March 11, 2012 Nucleosides are required for DNA and RNA synthesis, and the nucleoside adenosine has a function in a variety of signalling processes. Transport of nucleosides across cell membranes provides the major source of nucleosides in many cell types and is also res ... Full text Link to item Cite

Functional reconstitution of purified human Hv1 H+ channels.

Journal Article J Mol Biol · April 17, 2009 Voltage-dependent H(+) (Hv) channels mediate proton conduction into and out of cells under the control of membrane voltage. Hv channels are unusual compared to voltage-dependent K(+), Na(+), and Ca(2+) channels in that Hv channel genes encode a voltage sen ... Full text Link to item Cite

Two separate interfaces between the voltage sensor and pore are required for the function of voltage-dependent K(+) channels.

Journal Article PLoS Biol · March 3, 2009 Voltage-dependent K(+) (Kv) channels gate open in response to the membrane voltage. To further our understanding of how cell membrane voltage regulates the opening of a Kv channel, we have studied the protein interfaces that attach the voltage-sensor domai ... Full text Link to item Cite

Two separate interfaces between the Voltage sensor and pore are required for the function of Voltage-dependent K+ channels

Journal Article PLoS Biology · March 1, 2009 Voltage-dependent K+(Kv) channels gate open in response to the membrane voltage. To further our understanding of how cell membrane voltage regulates the opening of a Kv channel, we have studied the protein interfaces that attach the voltage-sensor domains ... Full text Cite

Dimeric subunit stoichiometry of the human voltage-dependent proton channel Hv1.

Journal Article Proc Natl Acad Sci U S A · June 3, 2008 In voltage-gated Na(+), K(+), and Ca(2+) channels, four voltage-sensor domains operate on a central pore domain in response to membrane voltage. In contrast, the voltage-gated proton channel (Hv) contains only a voltage-sensor domain, lacking a separate po ... Full text Link to item Cite

Structure of the KvAP voltage-dependent K+ channel and its dependence on the lipid membrane.

Journal Article Proc Natl Acad Sci U S A · October 25, 2005 Voltage-dependent ion channels gate open in response to changes in cell membrane voltage. This form of gating permits the propagation of action potentials. We present two structures of the voltage-dependent K(+) channel KvAP, in complex with monoclonal Fv ... Full text Link to item Cite

Structure and hydride transfer mechanism of a moderate thermophilic dihydrofolate reductase from Bacillus stearothermophilus and comparison to its mesophilic and hyperthermophilic homologues.

Journal Article Biochemistry · August 30, 2005 Dihydrofolate reductase (DHFR) from a moderate thermophilic organism, Bacillus stearothermophilus, has been cloned and expressed. Physical characterization of the protein (BsDHFR) indicates that it is a monomeric protein with a molecular mass of 18,694.6 D ... Full text Link to item Cite

YbiV from Escherichia coli K12 is a HAD phosphatase.

Journal Article Proteins · March 1, 2005 The protein YbiV from Escherichia coli K12 MG1655 is a hypothetical protein with sequence homology to the haloacid dehalogenase (HAD) superfamily of proteins. Although numerous members of this family have been identified, the functions of few are known. Us ... Full text Link to item Cite

A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom.

Journal Article Nature · July 8, 2004 Venomous animals produce small protein toxins that inhibit ion channels with high affinity. In several well-studied cases the inhibitory proteins are water-soluble and bind at a channel's aqueous-exposed extracellular surface. Here we show that a voltage-s ... Full text Link to item Cite

Regulation of the transcriptional activator NtrC1: structural studies of the regulatory and AAA+ ATPase domains.

Journal Article Genes Dev · October 15, 2003 Transcription by sigma54 RNA polymerase depends on activators that contain ATPase domains of the AAA+ class. These activators, which are often response regulators of two-component signal transduction systems, remodel the polymerase so that it can form open ... Full text Link to item Cite

High-resolution solution structure of the beryllofluoride-activated NtrC receiver domain.

Journal Article Biochemistry · August 5, 2003 Bacterial receiver domains mediate the cellular response to environmental changes through conformational changes induced by phosphorylation of a conserved aspartate residue. While the structures of several activated receiver domains have recently been dete ... Full text Link to item Cite

The NMR solution structure of BeF(3)(-)-activated Spo0F reveals the conformational switch in a phosphorelay system.

Journal Article J Mol Biol · August 1, 2003 Two-component systems, which are comprised of a single histidine-aspartate phosphotransfer module, are the dominant signaling pathways in bacteria and have recently been identified in several eukaryotic organisms as well. A tandem connection of two or more ... Full text Link to item Cite

Detection and characterization of xenon-binding sites in proteins by 129Xe NMR spectroscopy.

Journal Article J Mol Biol · September 13, 2002 Xenon-binding sites in proteins have led to a number of applications of xenon in biochemical and structural studies. Here we further develop the utility of 129Xe NMR in characterizing specific xenon-protein interactions. The sensitivity of the 129Xe chemic ... Full text Link to item Cite

Crystal structure of activated CheY. Comparison with other activated receiver domains.

Journal Article J Biol Chem · May 11, 2001 The crystal structure of BeF(3)(-)-activated CheY, with manganese in the magnesium binding site, was determined at 2.4-A resolution. BeF(3)(-) bonds to Asp(57), the normal site of phosphorylation, forming a hydrogen bond and salt bridge with Thr(87) and Ly ... Full text Link to item Cite

Crystal structure of an activated response regulator bound to its target.

Journal Article Nat Struct Biol · January 2001 The chemotactic regulator CheY controls the direction of flagellar rotation in Escherichia coli. We have determined the crystal structure of BeF3--activated CheY from E. coli in complex with an N-terminal peptide derived from its target, FliM. The structur ... Full text Link to item Cite

NMR structure of activated CheY.

Journal Article J Mol Biol · March 31, 2000 The CheY protein is the response regulator in bacterial chemotaxis. Phosphorylation of a conserved aspartyl residue induces structural changes that convert the protein from an inactive to an active state. The short half-life of the aspartyl-phosphate has p ... Full text Link to item Cite

Beryllofluoride mimics phosphorylation of NtrC and other bacterial response regulators.

Journal Article Proc Natl Acad Sci U S A · December 21, 1999 Two-component systems, sensor kinase-response regulator pairs, dominate bacterial signal transduction. Regulation is exerted by phosphorylation of an Asp in receiver domains of response regulators. Lability of the acyl phosphate linkage has limited structu ... Full text Link to item Cite

Solution structure of a sweet protein single-chain monellin determined by nuclear magnetic resonance and dynamical simulated annealing calculations.

Journal Article Biochemistry · February 23, 1999 Single-chain monellin (SCM), which is an engineered 94-residue polypeptide, has proven to be as sweet as native two-chain monellin. SCM is more stable than the native monellin for both heat and acidic environments. Data from gel filtration HPLC and NMR ind ... Full text Link to item Cite

Two-dimensional crystallization and projection structure of KcsA potassium channel.

Journal Article J Mol Biol · September 18, 1998 Potassium channels are integral membrane proteins that play a crucial role in regulating diverse cell functions in both electrically excitable and non-excitable cells. Molecular cloning has revealed a diverse family of genes that encode these proteins, and ... Full text Link to item Cite