Abstract:
:Venomous organisms have evolved a variety of structurally diverse peptide neurotoxins that target ion channels. Despite the lack of any obvious structural homology, unrelated toxins that interact with voltage-activated K(+) channels share a dyad motif composed of a lysine and a hydrophobic amino acid residue, usually a phenylalanine or a tyrosine. kappaM-Conotoxin RIIIK (kappaM-RIIIK), recently characterized from the cone snail Conus radiatus, blocks Shaker and TSha1 K(+) channels. The functional and structural study presented here reveals that kappaM-conotoxin RIIIK blocks voltage-activated K(+) channels with a novel pharmacophore that does not comprise a dyad motif. Despite the quite different amino acid sequence and no overlap in the pharmacological activity, we found that the NMR solution structure of kappaM-RIIIK in the C-terminal half is highly similar to that of mu-conotoxin GIIIA, a specific blocker of the skeletal muscle Na(+) channel Na(v)1.4. Alanine substitutions of all non-cysteine residues indicated that four amino acids of kappaM-RIIIK (Leu1, Arg10, Lys18, and Arg19) are key determinants for interaction with K(+) channels. Following the hypothesis that Leu1, the major hydrophobic amino acid determinant for binding, serves as the hydrophobic partner of a dyad motif, we investigated the effect of several mutations of Leu1 on the biological function of kappaM-RIIIK. Surprisingly, both the structural and mutational analysis suggested that, uniquely among well-characterized K(+) channel-targeted toxins, kappaM-RIIIK blocks voltage-gated K(+) channels with a pharmacophore that is not organized around a lysine-hydrophobic amino acid dyad motif.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Al-Sabi A,Lennartz D,Ferber M,Gulyas J,Rivier JE,Olivera BM,Carlomagno T,Terlau Hdoi
10.1021/bi0495681subject
Has Abstractpub_date
2004-07-13 00:00:00pages
8625-35issue
27eissn
0006-2960issn
1520-4995journal_volume
43pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Histone redistributions between endogenous DNA in calf thymus chromatin and exogenous DNA from Clostridium perfringens (69% A + T) or from Micrococcus luteus (30% A + T) induced by 0.6 M NaCl or by 2% formaldehyde were studied by thermal denaturation. The observed redistribution occurred on histone Hl when the exogeno...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00666a002
更新日期:1976-10-19 00:00:00
abstract::We have systematically validated the activity and inhibition of a HIV-1 protease (PR) variant bearing 17 mutations (PR(S17)), selected to represent high resistance by machine learning on genotype-phenotype data. Three of five mutations in PR(S17) correlating with major drug resistance, M46L, G48V, and V82S, and five o...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.6b00012
更新日期:2016-04-26 00:00:00
abstract::RNA helicase DHX33 has been shown to participate in a variety of cellular activities, including ribosome biogenesis, protein translation, and gene transcription. We and others further discovered that DHX33 is strongly expressed in several types of human cancers and plays important roles in promoting cancer cell prolif...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/acs.biochem.8b00166
更新日期:2019-01-29 00:00:00
abstract::Atomic resolution ( journal_title:Biochemistry pub_type: 杂志文章 doi:10.1021/bi0517133 更新日期:2006-02-21 00:00:00
abstract::There is no complete understanding of how serine protease inhibitors of the serpin family inhibit their target enzymes. Structural and biochemical studies have suggested that serpins utilize a mechanism that is distinct from the standard mechanism of inhibition proposed for most small protein protease inhibitors. Prot...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi960233w
更新日期:1996-06-11 00:00:00
abstract::The secretion of lung surfactant in alveolar type II cells is a complex process involving the fusion of lamellar bodies with the plasma membrane. This process is somewhat different from the exocytosis of hormones and neurotransmitters. For example, it is a relatively slower process, and lamellar bodies are very large ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi036338y
更新日期:2004-03-30 00:00:00
abstract::Transferrins have been extensively studied in order to understand how they reversibly bind and release iron. Human serum transferrin (hTF) is a single polypeptide chain that folds into two lobes (N- and C-lobe); each lobe binds a single ferric ion. Iron release induces a large conformational change in each lobe. At th...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi602425c
更新日期:2007-09-18 00:00:00
abstract::Isothermal titration calorimetry (ITC) is a powerful technique for investigating self-association processes of protein complexes and was expected to reveal quantitative data on peroxiredoxin oligomerization by directly measuring the thermodynamic parameters of dimer-dimer interaction. Recombinant classical 2-cysteine ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi8002956
更新日期:2008-07-08 00:00:00
abstract::DNA topoisomerase II is believed to be the enzyme that produces the protein-associated DNA strand breaks observed in mammalian cell nuclei treated with various intercalating agents. Two intercalators--4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA, amsacrine) and 2-methyl-9-hydroxyellipticinium (2-Me-9-OH-E+)-...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00344a015
更新日期:1985-11-05 00:00:00
abstract::Most proteins are denatured by heat treatment, and the process is usually irreversible. However, some proteins, such as hyperthermophilic proteins are known to be stable even at the boiling temperature of water. We here describe a systematic investigation of thermal behavior of proteins by purifying and characterizing...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi001441y
更新日期:2000-12-05 00:00:00
abstract::Heme-copper oxidases are membrane-bound proteins that catalyze the reduction of O(2) to H(2)O, a highly exergonic reaction. Part of the free energy of this reaction is used for pumping of protons across the membrane. The ba(3) oxidase from Thermus thermophilus presumably uses a single proton pathway for the transfer o...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi300132t
更新日期:2012-06-05 00:00:00
abstract::Here, we biochemically characterize Dictyostelium myosin II mutants that were previously phenotypically selected following random mutagenesis and shown to lie in the actin binding domain [Patterson, B., & Spudich, J. A. (1996) Genetics 143, 801-810]. We show that the conditional loss of myosin-dependent activity in vi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi963141f
更新日期:1997-07-15 00:00:00
abstract::The HIV-1 fusion peptide serves as a useful model system for understanding viral/target cell fusion, at least to the lipid-mixing stage. Previous solid-state NMR studies have shown that the membrane-bound HIV-1 fusion peptide adopts an extended conformation in a lipid mixture close to that of host cells of the virus. ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0348157
更新日期:2003-10-14 00:00:00
abstract::The three catalytic sites of the F(O)F(1) ATP synthase interact through a cooperative mechanism that is required for the promotion of catalysis. Replacement of the conserved alpha subunit Arg-376 in the Escherichia coli F(1) catalytic site with Ala or Lys resulted in turnover rates of ATP hydrolysis that were 2 x 10(3...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi992530h
更新日期:2000-03-14 00:00:00
abstract::Alzheimer's disease (AD) paired helical filaments (PHFs), building blocks of neurofibrillary tangles (NFTs) are composed of hyperphosphorylated forms of the microtubule-associated protein tau (i.e., PHF-tau). Currently, much effort is devoted to the development of diagnostic antibodies specific for PHF-tau since eleva...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi970380+
更新日期:1997-07-01 00:00:00
abstract::Further to our studies on the Escherichia coli 30S ribosomal subunit, the detailed surface topography of both 50S subunits and 70S ribosomes has been investigated by using iodination catalyzed by immobilized lactoperoxidase as the surface probe. In the 50S subunit, only proteins L2, L5, L10, and L11 were iodinated to ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00282a019
更新日期:1983-06-21 00:00:00
abstract::The integral membrane protein diacylglycerol kinase (DGK) from Escherichia coli has been reversibly unfolded in a protein/detergent/mixed micelle system by varying the molar ratio of n-decyl beta-D-maltoside (DM) and sodium dodecyl sulfate (SDS). Unfolding was monitored by circular dichroism (CD) and ultraviolet (UV) ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi963095j
更新日期:1997-05-13 00:00:00
abstract::An RNA that replicates with core RNA polymerase from E. coli and the substrates ATP, CTP, ITP, and UTP, was selected from a random poly(A,U,I,C) library and named EcorpI. Another replicating RNA, EcorpG, was obtained by template-free incubation of holo RNA polymerase and the substrates ATP, CTP, GTP, and UTP. Both RNA...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi002756g
更新日期:2001-03-20 00:00:00
abstract::The effect of anions on the stability of different functional conformations of Hb is examined through the determination of the dependence of O(2) affinity on water activity (a(w)). The control of a(w) is effected by varying the sucrose osmolal concentration in the bathing solution according to the "osmotic stress" met...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9905361
更新日期:1999-09-07 00:00:00
abstract::Blood coagulation is initiated by Ca(2+)-dependent binding of coagulation factor VIIa (FVIIa) to its cofactor, tissue factor (TF). The TF:FVIIa complex activates factors IX and X, ultimately leading to the formation of thrombin and the coagulation of blood. FVII consists of an N-terminal gamma-carboxyglutamic-acid-con...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi980522f
更新日期:1998-07-28 00:00:00
abstract::Methyl-coenzyme M reductase (MCR) catalyzes the methane-forming step in methanogenic archaea. The active enzyme harbors the nickel(I) hydrocorphin coenzyme F-430 as a prosthetic group and catalyzes the reversible reduction of methyl-coenzyme M (CH3-S-CoM) with coenzyme B (HS-CoM) to methane and CoM-S-S-CoB. MCR is als...
journal_title:Biochemistry
pub_type: 杂志文章,评审
doi:10.1021/acs.biochem.9b00164
更新日期:2019-12-31 00:00:00
abstract::The gamma-phosphoryl groups of two intermediates (M-ATP and M-ADP-P1) in the pathway of MgATP hydrolysis by myosin undergo extensive oxygen exchange with water. Actin activates the overall rate of hydrolysis at a rate-limiting step which follows these exchange reactions. Thus, actin, by decreasing the turnover time of...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00620a022
更新日期:1977-01-11 00:00:00
abstract::We extended the technique of frequency-domain fluorometry to an upper frequency limit of 2000 MHz. This was accomplished by using the harmonic content of a laser pulse train (3.76 MHz, 5 ps) from a synchronously pumped and cavity-dumped dye laser. We used a microchannel plate photomultiplier as the detector to obtain ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00375a012
更新日期:1987-01-13 00:00:00
abstract::The natural product hypericin is a photosensitive polycyclic aromatic dione compound, which has been widely investigated because of its virucidal and antitumor properties. Although it has been suggested that singlet oxygen or a radical species might be responsible for its biological action, its mechanism of action rem...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991147+
更新日期:1999-08-31 00:00:00
abstract::Human lysosomal enzymes acid-beta-glucosidase (GCase) and acid-alpha-galactosidase (alpha-Gal A) hydrolyze the sphingolipids glucosyl- and globotriaosylceramide, respectively, and mutations in these enzymes lead to the lipid metabolism disorders Gaucher and Fabry disease, respectively. We have investigated the structu...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9002265
更新日期:2009-06-09 00:00:00
abstract::NADPH-cytochrome P450 oxidoreductase (P450 reductase, EC 1.6.2.4) is an essential component of the P450 monooxygenase complex and binds FMN, FAD, and NADPH cofactors. Residues Tyr140 and Tyr178 are known to be involved in FMN binding. A third aromatic side chain, Phe181, is also located in the proximity of the FMN rin...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi011147l
更新日期:2001-11-13 00:00:00
abstract::N-Ethylmaleimide modified heavy meromyosin in only 3-fold activated by actin rather than 200-fold as is normal heavy meromyosin (Silverman, R., Eisenberg, E., and Kielley, W. W. (1972), Nature (London) 240, 207). Ultracentrifuge studies demonstrated that in the absence of ATP the N-ethylmaleimide modified heavy merom...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00688a020
更新日期:1975-08-26 00:00:00
abstract::Human prolactin (hPRL) binds two human prolactin receptor molecules, creating active heterotrimeric complexes. Receptors bind dissimilar hormone surfaces termed site 1 and site 2 in an obligate ordered process. We sought to map the functional epitopes in site 1 of hPRL. Extensive alanine mutagenesis (102 of the 199 re...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi101838s
更新日期:2011-03-01 00:00:00
abstract::The aryl hydrocarbon receptor (AhR) is an intracellular receptor protein that regulates gene transcription in response to both man-made and natural ligands. A modular transactivaton domain (TAD) has been mapped to the 304 C-terminal amino acids and consists of acidic, Q-rich, and P/S/T-rich subdomains. We have used st...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0487701
更新日期:2005-01-18 00:00:00
abstract::The three-dimensional structure of the bifunctional alpha-amylase/trypsin inhibitor (RBI) from seeds of ragi (Eleusine coracana Gaertneri) has been determined in solution using multidimensional 1H and 15N NMR spectroscopy. The inhibitor consists of 122 amino acids, with 5 disulfide bridges, and belongs to the plant al...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00026a009
更新日期:1995-07-04 00:00:00