Maxim Dubinnyi - Academia.edu (original) (raw)
Papers by Maxim Dubinnyi
Journal of Biological Chemistry, 2012
Background: ASIC3 channels contribute to pain stimuli perception. Results: A new compound (sevano... more Background: ASIC3 channels contribute to pain stimuli perception. Results: A new compound (sevanol) was isolated from thyme extract and was shown to inhibit ASIC3 current components. Conclusion: Sevanol could play a considerable role in thyme analgesic properties. Significance: The data on the structure and potency of sevanol can make a contribution to understanding the function of ASIC3 and can be helpful for developing other pharmacological substances targeting ASIC3. . The abbreviations used are: ASIC, acid-sensing ion channel; CFA, complete Freund's adjuvant; DMSO, dimethyl sulfoxide; LC-ESI-MS, liquid chromatography-mass spectrometry with electrospray ionization; p2X3, purinegated cation channel type 3; TRPV1, transient receptor potential vanilloid type 1; HSQC, heteronuclear single quantum correlation; HMBC, heteronuclear multiple bond correlation; ROESY, rotating-frame nuclear Overhauser effect correlation spectroscopy.
Mendeleev Communications, 2016
Angewandte Chemie, 2015
A novel luciferin from a bioluminescent Siberian earthworm Fridericia heliota was recently descri... more A novel luciferin from a bioluminescent Siberian earthworm Fridericia heliota was recently described. In this study, the Fridericia oxyluciferin was isolated and its structure elucidated. The results provide insight into a novel bioluminescence mechanism in nature. Oxidative decarboxylation of a lysine fragment of the luciferin supplies energy for light generation, while a fluorescent CompX moiety remains intact and serves as the light emitter.
Mendeleev Communications, 2015
Mendeleev Commun., 2015, 25, 99-100 -99 -Mendeleev Communications
![Research paper thumbnail of [Lys35 spin-labeled cytotoxin II from Naja oxiana venom for study of its interaction with phospholipid membranes by EPR]](https://attachments.academia-assets.com/46832284/thumbnails/1.jpg)
](Bioorganicheskaia khimiia, 1999
Cytotoxin II from the venom of the Central-Asian cobra Naja oxiana spin-labeled at Lys35 (SLCT II... more Cytotoxin II from the venom of the Central-Asian cobra Naja oxiana spin-labeled at Lys35 (SLCT II) was studied by ESR spectroscopy in aqueous solution and upon interaction with phospholipid vesicles from egg phosphatidylcholine or its mixture with dimyristoylphosphatidylglycerol (molar ratio 9 : 1). The distribution of SLCT II between the aqueous and lipid phases depended on the toxin and lipid concentrations and on the solution ionic strength. It was analyzed using the modified Gouy-Chapman theory that takes into account different charges of the cytotoxin in solution and in membrane. The analysis revealed two states of the cytotoxin-lipid complex. The first state corresponds to monomeric SLCT II hydrophobically interacting with the lipid membrane [a binding constant of (8 ± 3) × 10 3 å -1 ] and carrying the charge of 4.4 ± 0.3 . On the basis of these parameters and the spatial structure of cytotoxin II in dodecylphosphocholine micelles, we concluded that the cytotoxin is mainly incorporated into the region of polar groups of the lipid bilayer. The second state of SLCT II is realized at high cytotoxin concentrations in the membrane and corresponds to the formation of toxin-lipid complexes that disorganize the membrane bilayer structure.
Chemistry - A European Journal, 2015
Novel Peptide Chemistry Unusual peptides revealing a novel class of natural products were found i... more Novel Peptide Chemistry Unusual peptides revealing a novel class of natural products were found in the luminescent earthworms Fridericia heliota from Siberian taiga. The structures of these peptides give clues for understanding biosynthetic pathway for a recently described Fridericia luciferin. For more information see the Full Paper by I. V. Yampolsky et al. on page 3942 ff.
Chemistry - A European Journal, 2015
We report isolation and structure elucidation of AsLn5, AsLn7, AsLn11 and AsLn12: novel luciferin... more We report isolation and structure elucidation of AsLn5, AsLn7, AsLn11 and AsLn12: novel luciferin analogs from the bioluminescent earthworm Fridericia heliota. They were found to be highly unusual modified peptides, comprising either of the two tyrosine-derived chromophores, CompX or CompY and a set of amino acids, including threonine, gamma-aminobutyric acid, homoarginine, and unsymmetrical N,N-dimethylarginine. These natural compounds represent a unique peptide chemistry found in terrestrial animals and rise novel questions concerning their biosynthetic origin.
RSC Adv., 2014
ABSTRACT Ozonolysis of furocoumarins followed by reductive work-up yields not only common symmetr... more ABSTRACT Ozonolysis of furocoumarins followed by reductive work-up yields not only common symmetrical dialdehydes, but also o- formylumbelliferones with moderate-to-high yields. Simultaneous formation of both products is accounted for the transformation of carbonyl oxides – products of primary ozonide ring opening.
Russian Journal of Bioorganic Chemistry, 2001
Cytotoxin II from the venom of the Central-Asian cobra Naja oxiana spin-labeled at Lys35 (SLCT II... more Cytotoxin II from the venom of the Central-Asian cobra Naja oxiana spin-labeled at Lys35 (SLCT II) was studied by ESR spectroscopy in aqueous solution and upon interaction with phospholipid vesicles from egg phosphatidylcholine or its mixture with dimyristoylphosphatidylglycerol (molar ratio 9 : 1). The distribution of SLCT II between the aqueous and lipid phases depended on the toxin and lipid concentrations and on the solution ionic strength. It was analyzed using the modified Gouy-Chapman theory that takes into account different charges of the cytotoxin in solution and in membrane. The analysis revealed two states of the cytotoxin-lipid complex. The first state corresponds to monomeric SLCT II hydrophobically interacting with the lipid membrane [a binding constant of (8 ± 3) × 10 3 å -1 ] and carrying the charge of 4.4 ± 0.3 . On the basis of these parameters and the spatial structure of cytotoxin II in dodecylphosphocholine micelles, we concluded that the cytotoxin is mainly incorporated into the region of polar groups of the lipid bilayer. The second state of SLCT II is realized at high cytotoxin concentrations in the membrane and corresponds to the formation of toxin-lipid complexes that disorganize the membrane bilayer structure.
European Journal of Biochemistry, 2003
Biochem. Moscow Suppl. Ser. A, 2013
Receptor tyrosine kinases (RTKs) play an important role in intercellular signal transduction thro... more Receptor tyrosine kinases (RTKs) play an important role in intercellular signal transduction through the plasma membrane. RTKs are integral membrane proteins activated upon lateral homo or het erodimerization involving their transmembrane domain. The polymorphism and mutations in RTK trans membrane (TM) domains are directly associated with a number of human diseases. The family of epidermal growth factor receptors, ErbB, is an important class of RTKs participating in human cell growth, develop ment, and differentiation. In order to investigate the influence of pathogenic mutations in ErbB TM domains on the structural and dynamic properties of these receptors and on specific interactions of their TM domains, we have developed highly effective systems of bacterial expression and purification of recombinant trans membrane fragments ErbB2 641 684 with pro oncogenic substitution of Val 659 by Glu or Gln. Transmembrane fragments were obtained in Escherichia coli BL21 (DE3) pLysS as a fusion protein with thioredoxin A. The purification protocol includes immobilized metal ion affinity chromatography (IMAC) and cation exchange chromatography. The application of the protease Thrombin for hybrid protein hydrolysis considerably reduces financial expenditure as compared to the analogous protocols. The described techniques allow obtaining the milligram quantities of ErbB2 transmembrane fragments and its 15 N /[ 15 N, 13 C] isotope labeled derivatives for the analysis of their spatial structure using high resolution heteronuclear NMR spec troscopy in a membrane mimicking milieu.
Tetrahedron Letters, 2014
A luciferin analog, CompX, was isolated from the extracts of the bioluminescent earthworm Frideri... more A luciferin analog, CompX, was isolated from the extracts of the bioluminescent earthworm Fridericia heliota. Its structure was determined as (Z)-5-(2-carboxy-2-methoxyvinyl)-2-hydroxybenzoic acid by spectroscopic data analysis and was confirmed by total synthesis. The (Z)-configuration of the double bond was established by comparing the ROESY spectra of CompX with those of its synthetic (E)-isomer. CompX represents a tyrosine analog, not previously found in natural sources, and is probably derived from tyrosine by deamination, O-methylation of the resulting alpha-keto acid, and carboxylation at the aromatic core.
Solid State Nuclear Magnetic Resonance, 2006
31 P-NMR spectroscopy is widely used for studies of phospholipid liposomes, a commonly used model... more 31 P-NMR spectroscopy is widely used for studies of phospholipid liposomes, a commonly used model of a biological membrane. For the correct analysis of 31 P-NMR spectra of the liposomes it is necessary to take into account that they are deformed by the magnetic field of the spectrometer. The liposomes become ellipsoidal and this affects the lineshape of the spectrum. In the present communication we suggest a new analytical formula for modeling of 31 P-NMR spectra of the prolate phospholipid liposomes. The formula assumes a Lorentzian broadening function and exactly ellipsoidal shape of the liposomes. Based on the formula a program called P-FIT is designed for the practical analysis of the experimental multicomponent spectra of the prolate liposomes. The versatility of the program developed in a Mathematica environment is demonstrated by simulations of a number of 31 P-NMR spectra with different complexity. r 2005 Elsevier Inc. All rights reserved. Keywords: 31 P-NMR spectroscopy; Prolate phospholipid liposomes; Deformation by the magnetic field; Modeling of NMR spectra; Analytical formula for spectrum lineshape; Mathematica (Wolfram research) ARTICLE IN PRESS www.elsevier.com/locate/ssnmr 0926-2040/$ -see front matter r Abbreviations: CSA, chemical shift anisotropy; DPPG, dipalmitoylphosphatidylglycerol; PPL, prolate phospholipid liposomes; FID, free induction decay à Corresponding author. Fax: +7 095 335 50 33. E-mail address: aars@nmr.ru (A.S. Arseniev).
Journal of the American Chemical Society, 2010
The structure and dynamics of the isolated voltage-sensing domain (VSD) of the archaeal potassium... more The structure and dynamics of the isolated voltage-sensing domain (VSD) of the archaeal potassium channel KvAP was studied by high-resolution NMR. The almost complete backbone resonance assignment and partial side-chain assignment of the 2 H, 13 C, 15 N-labeled VSD were obtained for the protein domain solubilized in DPC/LDAO (2:1) mixed micelles. Secondary and tertiary structures of the VSD were characterized using secondary chemical shifts and NOE contacts. These data indicate that the spatial structure of the VSD solubilized in micelles corresponds to the structure of the domain in an open state of the channel. NOE contacts and secondary chemical shifts of amide protons indicate the presence of tightly bound water molecule as well as hydrogen bond formation involving an interhelical salt bridge (Asp62-R133) that stabilizes the overall structure of the domain. The backbone dynamics of the VSD was studied using 15 N relaxation measurements. The loop regions S1-S2 and S2-S3 were found mobile, while the S3-S4 loop (voltage-sensor paddle) was found stable at the ps-ns time scale. The moieties of S1, S2, S3, and S4 helices sharing interhelical contacts (at the level of the Asp62-R133 salt bridge) were observed in conformational exchange on the µs-ms time scale. Similar exchange-induced broadening of characteristic resonances was observed for the VSD solubilized in the membrane of lipid-protein nanodiscs composed of DMPC, DMPG, and POPC/DOPG lipids. Apparently, the observed interhelical motions represent an inherent property of the VSD of the KvAP channel and can play an important role in the voltage gating.
Journal of Biological Chemistry, 2012
A novel compound was identified in the acidic extract of Thymus armeniacus collected in the Lake ... more A novel compound was identified in the acidic extract of Thymus armeniacus collected in the Lake Sevan region of Armenia. This compound, named "sevanol," to our knowledge is the first low molecular weight natural molecule that has a reversible inhibition effect on both the transient and the sustained current of human ASIC3 channels expressed in Xenopus laevis oocytes. Sevanol completely blocked the transient component (IC(50) 353 ± 23 μM) and partially (∼45%) inhibited the amplitude of the sustained component (IC(50) of 234 ± 53 μM). Other types of acid-sensing ion channel (ASIC) channels were intact to sevanol application, except ASIC1a, which showed more than six times less affinity to it as compared with the inhibitory action on the ASIC3 channel. To elucidate the structure of sevanol, the set of NMR spectra in two solvents (d(6)-DMSO and D(2)O) was collected, and the complete chemical structure was confirmed by liquid chromatography-mass spectrometry with electrospray ionization (LC-ESI(+)-MS) fragmentation. This compound is a new lignan built up of epiphyllic acid and two isocitryl esters in positions 9 and 10. In vivo administration of sevanol (1-10 mg/kg) significantly reversed thermal hyperalgesia induced by complete Freund's adjuvant injection and reduced response to acid in a writhing test. Thus, we assume the probable considerable role of sevanol in known analgesic and anti-inflammatory properties of thyme.
Cytotoxins are positively charged polypeptides that constitute about 60% of all proteins in cobra... more Cytotoxins are positively charged polypeptides that constitute about 60% of all proteins in cobra venom; they have a wide spectrum of biological activities. By CD spectroscopy, cytotoxins CT1 and CT2 Naja oxiana, CT3 Naja kaouthia, and CT1 and CT2 Naja haje were shown to have similar secondary structure in an aqueous environment, with dominating beta-sheet structure, and to vary in the twisting angle of the beta-sheet and the conformation of disulfide groups. Using dodecylphosphocholine micelles and liposomes, CT1 and CT2 Naja oxiana were shown to incorporate into lipid structures without changes in the secondary structure of the peptides. The binding of CT1 and CT2 Naja oxiana with liposomes was associated with an increase in the beta-sheet twisting and a sign change of the dihedral angle of one disulfide group. The cytotoxins were considerably different in cytotoxicity and cooperativity of the effect on human promyelocytic leukemia cells HL60, mouse myelomonocytic cells WEHI-3, an...
Journal of Biological Chemistry, 2012
Background: ASIC3 channels contribute to pain stimuli perception. Results: A new compound (sevano... more Background: ASIC3 channels contribute to pain stimuli perception. Results: A new compound (sevanol) was isolated from thyme extract and was shown to inhibit ASIC3 current components. Conclusion: Sevanol could play a considerable role in thyme analgesic properties. Significance: The data on the structure and potency of sevanol can make a contribution to understanding the function of ASIC3 and can be helpful for developing other pharmacological substances targeting ASIC3. . The abbreviations used are: ASIC, acid-sensing ion channel; CFA, complete Freund's adjuvant; DMSO, dimethyl sulfoxide; LC-ESI-MS, liquid chromatography-mass spectrometry with electrospray ionization; p2X3, purinegated cation channel type 3; TRPV1, transient receptor potential vanilloid type 1; HSQC, heteronuclear single quantum correlation; HMBC, heteronuclear multiple bond correlation; ROESY, rotating-frame nuclear Overhauser effect correlation spectroscopy.
Mendeleev Communications, 2016
Angewandte Chemie, 2015
A novel luciferin from a bioluminescent Siberian earthworm Fridericia heliota was recently descri... more A novel luciferin from a bioluminescent Siberian earthworm Fridericia heliota was recently described. In this study, the Fridericia oxyluciferin was isolated and its structure elucidated. The results provide insight into a novel bioluminescence mechanism in nature. Oxidative decarboxylation of a lysine fragment of the luciferin supplies energy for light generation, while a fluorescent CompX moiety remains intact and serves as the light emitter.
Mendeleev Communications, 2015
Mendeleev Commun., 2015, 25, 99-100 -99 -Mendeleev Communications
Bioorganicheskaia khimiia, 1999
Cytotoxin II from the venom of the Central-Asian cobra Naja oxiana spin-labeled at Lys35 (SLCT II... more Cytotoxin II from the venom of the Central-Asian cobra Naja oxiana spin-labeled at Lys35 (SLCT II) was studied by ESR spectroscopy in aqueous solution and upon interaction with phospholipid vesicles from egg phosphatidylcholine or its mixture with dimyristoylphosphatidylglycerol (molar ratio 9 : 1). The distribution of SLCT II between the aqueous and lipid phases depended on the toxin and lipid concentrations and on the solution ionic strength. It was analyzed using the modified Gouy-Chapman theory that takes into account different charges of the cytotoxin in solution and in membrane. The analysis revealed two states of the cytotoxin-lipid complex. The first state corresponds to monomeric SLCT II hydrophobically interacting with the lipid membrane [a binding constant of (8 ± 3) × 10 3 å -1 ] and carrying the charge of 4.4 ± 0.3 . On the basis of these parameters and the spatial structure of cytotoxin II in dodecylphosphocholine micelles, we concluded that the cytotoxin is mainly incorporated into the region of polar groups of the lipid bilayer. The second state of SLCT II is realized at high cytotoxin concentrations in the membrane and corresponds to the formation of toxin-lipid complexes that disorganize the membrane bilayer structure.
Chemistry - A European Journal, 2015
Novel Peptide Chemistry Unusual peptides revealing a novel class of natural products were found i... more Novel Peptide Chemistry Unusual peptides revealing a novel class of natural products were found in the luminescent earthworms Fridericia heliota from Siberian taiga. The structures of these peptides give clues for understanding biosynthetic pathway for a recently described Fridericia luciferin. For more information see the Full Paper by I. V. Yampolsky et al. on page 3942 ff.
Chemistry - A European Journal, 2015
We report isolation and structure elucidation of AsLn5, AsLn7, AsLn11 and AsLn12: novel luciferin... more We report isolation and structure elucidation of AsLn5, AsLn7, AsLn11 and AsLn12: novel luciferin analogs from the bioluminescent earthworm Fridericia heliota. They were found to be highly unusual modified peptides, comprising either of the two tyrosine-derived chromophores, CompX or CompY and a set of amino acids, including threonine, gamma-aminobutyric acid, homoarginine, and unsymmetrical N,N-dimethylarginine. These natural compounds represent a unique peptide chemistry found in terrestrial animals and rise novel questions concerning their biosynthetic origin.
RSC Adv., 2014
ABSTRACT Ozonolysis of furocoumarins followed by reductive work-up yields not only common symmetr... more ABSTRACT Ozonolysis of furocoumarins followed by reductive work-up yields not only common symmetrical dialdehydes, but also o- formylumbelliferones with moderate-to-high yields. Simultaneous formation of both products is accounted for the transformation of carbonyl oxides – products of primary ozonide ring opening.
Russian Journal of Bioorganic Chemistry, 2001
Cytotoxin II from the venom of the Central-Asian cobra Naja oxiana spin-labeled at Lys35 (SLCT II... more Cytotoxin II from the venom of the Central-Asian cobra Naja oxiana spin-labeled at Lys35 (SLCT II) was studied by ESR spectroscopy in aqueous solution and upon interaction with phospholipid vesicles from egg phosphatidylcholine or its mixture with dimyristoylphosphatidylglycerol (molar ratio 9 : 1). The distribution of SLCT II between the aqueous and lipid phases depended on the toxin and lipid concentrations and on the solution ionic strength. It was analyzed using the modified Gouy-Chapman theory that takes into account different charges of the cytotoxin in solution and in membrane. The analysis revealed two states of the cytotoxin-lipid complex. The first state corresponds to monomeric SLCT II hydrophobically interacting with the lipid membrane [a binding constant of (8 ± 3) × 10 3 å -1 ] and carrying the charge of 4.4 ± 0.3 . On the basis of these parameters and the spatial structure of cytotoxin II in dodecylphosphocholine micelles, we concluded that the cytotoxin is mainly incorporated into the region of polar groups of the lipid bilayer. The second state of SLCT II is realized at high cytotoxin concentrations in the membrane and corresponds to the formation of toxin-lipid complexes that disorganize the membrane bilayer structure.
European Journal of Biochemistry, 2003
Biochem. Moscow Suppl. Ser. A, 2013
Receptor tyrosine kinases (RTKs) play an important role in intercellular signal transduction thro... more Receptor tyrosine kinases (RTKs) play an important role in intercellular signal transduction through the plasma membrane. RTKs are integral membrane proteins activated upon lateral homo or het erodimerization involving their transmembrane domain. The polymorphism and mutations in RTK trans membrane (TM) domains are directly associated with a number of human diseases. The family of epidermal growth factor receptors, ErbB, is an important class of RTKs participating in human cell growth, develop ment, and differentiation. In order to investigate the influence of pathogenic mutations in ErbB TM domains on the structural and dynamic properties of these receptors and on specific interactions of their TM domains, we have developed highly effective systems of bacterial expression and purification of recombinant trans membrane fragments ErbB2 641 684 with pro oncogenic substitution of Val 659 by Glu or Gln. Transmembrane fragments were obtained in Escherichia coli BL21 (DE3) pLysS as a fusion protein with thioredoxin A. The purification protocol includes immobilized metal ion affinity chromatography (IMAC) and cation exchange chromatography. The application of the protease Thrombin for hybrid protein hydrolysis considerably reduces financial expenditure as compared to the analogous protocols. The described techniques allow obtaining the milligram quantities of ErbB2 transmembrane fragments and its 15 N /[ 15 N, 13 C] isotope labeled derivatives for the analysis of their spatial structure using high resolution heteronuclear NMR spec troscopy in a membrane mimicking milieu.
Tetrahedron Letters, 2014
A luciferin analog, CompX, was isolated from the extracts of the bioluminescent earthworm Frideri... more A luciferin analog, CompX, was isolated from the extracts of the bioluminescent earthworm Fridericia heliota. Its structure was determined as (Z)-5-(2-carboxy-2-methoxyvinyl)-2-hydroxybenzoic acid by spectroscopic data analysis and was confirmed by total synthesis. The (Z)-configuration of the double bond was established by comparing the ROESY spectra of CompX with those of its synthetic (E)-isomer. CompX represents a tyrosine analog, not previously found in natural sources, and is probably derived from tyrosine by deamination, O-methylation of the resulting alpha-keto acid, and carboxylation at the aromatic core.
Solid State Nuclear Magnetic Resonance, 2006
31 P-NMR spectroscopy is widely used for studies of phospholipid liposomes, a commonly used model... more 31 P-NMR spectroscopy is widely used for studies of phospholipid liposomes, a commonly used model of a biological membrane. For the correct analysis of 31 P-NMR spectra of the liposomes it is necessary to take into account that they are deformed by the magnetic field of the spectrometer. The liposomes become ellipsoidal and this affects the lineshape of the spectrum. In the present communication we suggest a new analytical formula for modeling of 31 P-NMR spectra of the prolate phospholipid liposomes. The formula assumes a Lorentzian broadening function and exactly ellipsoidal shape of the liposomes. Based on the formula a program called P-FIT is designed for the practical analysis of the experimental multicomponent spectra of the prolate liposomes. The versatility of the program developed in a Mathematica environment is demonstrated by simulations of a number of 31 P-NMR spectra with different complexity. r 2005 Elsevier Inc. All rights reserved. Keywords: 31 P-NMR spectroscopy; Prolate phospholipid liposomes; Deformation by the magnetic field; Modeling of NMR spectra; Analytical formula for spectrum lineshape; Mathematica (Wolfram research) ARTICLE IN PRESS www.elsevier.com/locate/ssnmr 0926-2040/$ -see front matter r Abbreviations: CSA, chemical shift anisotropy; DPPG, dipalmitoylphosphatidylglycerol; PPL, prolate phospholipid liposomes; FID, free induction decay à Corresponding author. Fax: +7 095 335 50 33. E-mail address: aars@nmr.ru (A.S. Arseniev).
Journal of the American Chemical Society, 2010
The structure and dynamics of the isolated voltage-sensing domain (VSD) of the archaeal potassium... more The structure and dynamics of the isolated voltage-sensing domain (VSD) of the archaeal potassium channel KvAP was studied by high-resolution NMR. The almost complete backbone resonance assignment and partial side-chain assignment of the 2 H, 13 C, 15 N-labeled VSD were obtained for the protein domain solubilized in DPC/LDAO (2:1) mixed micelles. Secondary and tertiary structures of the VSD were characterized using secondary chemical shifts and NOE contacts. These data indicate that the spatial structure of the VSD solubilized in micelles corresponds to the structure of the domain in an open state of the channel. NOE contacts and secondary chemical shifts of amide protons indicate the presence of tightly bound water molecule as well as hydrogen bond formation involving an interhelical salt bridge (Asp62-R133) that stabilizes the overall structure of the domain. The backbone dynamics of the VSD was studied using 15 N relaxation measurements. The loop regions S1-S2 and S2-S3 were found mobile, while the S3-S4 loop (voltage-sensor paddle) was found stable at the ps-ns time scale. The moieties of S1, S2, S3, and S4 helices sharing interhelical contacts (at the level of the Asp62-R133 salt bridge) were observed in conformational exchange on the µs-ms time scale. Similar exchange-induced broadening of characteristic resonances was observed for the VSD solubilized in the membrane of lipid-protein nanodiscs composed of DMPC, DMPG, and POPC/DOPG lipids. Apparently, the observed interhelical motions represent an inherent property of the VSD of the KvAP channel and can play an important role in the voltage gating.
Journal of Biological Chemistry, 2012
A novel compound was identified in the acidic extract of Thymus armeniacus collected in the Lake ... more A novel compound was identified in the acidic extract of Thymus armeniacus collected in the Lake Sevan region of Armenia. This compound, named "sevanol," to our knowledge is the first low molecular weight natural molecule that has a reversible inhibition effect on both the transient and the sustained current of human ASIC3 channels expressed in Xenopus laevis oocytes. Sevanol completely blocked the transient component (IC(50) 353 ± 23 μM) and partially (∼45%) inhibited the amplitude of the sustained component (IC(50) of 234 ± 53 μM). Other types of acid-sensing ion channel (ASIC) channels were intact to sevanol application, except ASIC1a, which showed more than six times less affinity to it as compared with the inhibitory action on the ASIC3 channel. To elucidate the structure of sevanol, the set of NMR spectra in two solvents (d(6)-DMSO and D(2)O) was collected, and the complete chemical structure was confirmed by liquid chromatography-mass spectrometry with electrospray ionization (LC-ESI(+)-MS) fragmentation. This compound is a new lignan built up of epiphyllic acid and two isocitryl esters in positions 9 and 10. In vivo administration of sevanol (1-10 mg/kg) significantly reversed thermal hyperalgesia induced by complete Freund's adjuvant injection and reduced response to acid in a writhing test. Thus, we assume the probable considerable role of sevanol in known analgesic and anti-inflammatory properties of thyme.
Cytotoxins are positively charged polypeptides that constitute about 60% of all proteins in cobra... more Cytotoxins are positively charged polypeptides that constitute about 60% of all proteins in cobra venom; they have a wide spectrum of biological activities. By CD spectroscopy, cytotoxins CT1 and CT2 Naja oxiana, CT3 Naja kaouthia, and CT1 and CT2 Naja haje were shown to have similar secondary structure in an aqueous environment, with dominating beta-sheet structure, and to vary in the twisting angle of the beta-sheet and the conformation of disulfide groups. Using dodecylphosphocholine micelles and liposomes, CT1 and CT2 Naja oxiana were shown to incorporate into lipid structures without changes in the secondary structure of the peptides. The binding of CT1 and CT2 Naja oxiana with liposomes was associated with an increase in the beta-sheet twisting and a sign change of the dihedral angle of one disulfide group. The cytotoxins were considerably different in cytotoxicity and cooperativity of the effect on human promyelocytic leukemia cells HL60, mouse myelomonocytic cells WEHI-3, an...