Abstract:
:To understand relationships between membrane-binding properties of cytolytic peptides and resulting cytotoxicity, we investigated interactions of dermaseptin analogues with model bilayers by means of surface plasmon resonance. First, we tested the system by comparing two native dermaseptins, S1 and S4, whose binding properties were previously characterized in different experimental systems. Validation experiments revealed deviations from the one-to-one interaction model and indicated the binding to proceed by a two-stage mechanism. By calculation of apparent affinity constants and individual affinities for both steps of the interaction, the biosensor technology was able to distinguish between surface-bound peptides that subsequently penetrated into the bilayer and peptides that remained essentially superficially bound. This data interpretation was sustained after analysis of a series of dermaseptin S4 derivatives whose binding data were compared with cytotoxicity, revealing cytolytic activity to correlate mainly with insertion affinity. The data indicate that the potency of highly cytolytic peptides such as K(4)K(20)-S4 is not due to the highest membrane adhesion affinity but to the highest propensity for the inserted state. Similarly, truncated derivatives of 16, 13, and 10 residues showed a progressive reduction in cytotoxicity that best correlated with progressive reduction in insertion affinity. Support for the adhesion versus inserted states was provided by proteolytic experiments with RBC-bound peptides that demonstrated K(4)K(20)-S4 to be protected from enzymatic cleavage, unlike its 13-mer derivative. Overall, using the two-stage model proved instrumental in investigating membrane-binding properties of antimicrobial peptides and capable of explaining the cytolytic properties of closely related analogues.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Gaidukov L,Fish A,Mor Adoi
10.1021/bi034514xsubject
Has Abstractpub_date
2003-11-11 00:00:00pages
12866-74issue
44eissn
0006-2960issn
1520-4995journal_volume
42pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic surface of oligodendrocyte membranes and is most likely responsible for adhesion of these surfaces in the multilayered myelin sheath. It can also polymerize actin, bundle F-actin filaments, and bind actin filaments to lipid bilayers through...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0519194
更新日期:2006-01-17 00:00:00
abstract::Aquifex aeolicus 3-deoxy-d-manno-octulosonate 8-phosphate synthase (KDO8PS) is active with a variety of different divalent metal ions bound in the active site. The Cd(2+), Zn(2+), and Cu(2+) substituted enzymes display similar values of k(cat) and similar dependence of K(m)(PEP) and K(m)(A5P) on both substrate and pro...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi801955h
更新日期:2009-04-28 00:00:00
abstract::The subgel phases of a homologous series of saturated straight-chain diacylphosphatidylcholines with hydrocarbon chains consisting of 10-18 carbon atoms were studied by Fourier-transform infrared spectroscopy. All of these lipids initially form a subgel phase which is spectroscopically similar to that obtained when fu...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00486a024
更新日期:1990-08-28 00:00:00
abstract::Ner repressors of the transposable phages Mu and D108 play a central role in regulating the expression of the early (transposase) operon and in ensuring that phage growth proceeds along a lytic pathway. The latter function is analogous to that performed by the Cro protein of phage lambda. Unlike lambda Cro, however, t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00201a018
更新日期:1994-09-06 00:00:00
abstract::Mammalian cGMP- and cAMP-dependent protein kinase show considerable similarity in amino acid sequence, although they specifically bind different cyclic nucleotides. Results of cGMP analogue binding experiments, combined with modeling of the cGMP binding sites by analogy to the structure of the homologous catabolite ge...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00440a059
更新日期:1989-07-11 00:00:00
abstract::Ultraviolet resonance Raman (RR) spectra, with 200- and 218-nm excitation from a H2-shifted quadrupled Nd:YAG laser, are reported for insulin and alpha-lactalbumin in dilute aqueous solution, at pH values known to produce differences in the exposure of the aromatic residues to solvent. At 200 nm, the spectra are domin...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00329a009
更新日期:1985-04-09 00:00:00
abstract::Recently, we described the formation of a complex between liposomes and the unfolded protein rhodanese (thiosulfate:cyanide sulfurtransferase, EC 2.8.1.1), which could be liberated and efficiently reactivated after treatment of the complex with detergents [Zardeneta, G., & Horowitz, P. M. (1992) Eur. J. Biochem. 210, ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00213a025
更新日期:1993-12-21 00:00:00
abstract::Binding studies of the interaction of immobilized 1alpha- and 17alpha-aminoalkyl derivatives of 5alpha-dihydrotestosterone (DHT) with purified N-deglycosylated homodimeric human sex hormone-binding globulin (SHBG) were performed using a surface plasmon resonance biosensor. These 1alpha- and 17alpha-derivatives with sp...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi035269k
更新日期:2003-11-25 00:00:00
abstract::The catalytic mechanism of valyl-tRNA synthetase from baker's yeast has been investigated by pre-steady-state and steady-state kinetic measurements and end product dissociation studies. The pre-steady-state kinetics show a lag period during the early time when the reaction is started with free enzyme. The preincubatio...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00511a001
更新日期:1981-04-14 00:00:00
abstract::The coordinated activity of protein tyrosine phosphatases (PTPs) is crucial for the initiation, modulation, and termination of diverse cellular processes. The catalytic activity of this protein depends on a nucleophilic cysteine at the active site that mediates the hydrolysis of the incoming phosphotyrosine substrate....
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi201092q
更新日期:2011-11-22 00:00:00
abstract::Three spin-labeled derivatives of the voltage-gated peptide alamethicin were prepared with nitroxides at the C-terminal phenyalaninol, and at positions 9 and 15 in the amino acid sequence. In addition, three spin-labeled derivatives of an analog of alamethicin where alpha-methylalanine residues are replaced by leucine...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi951985d
更新日期:1996-01-16 00:00:00
abstract::We have described earlier a chromatin-bound protease with unique specificity for histone H2A [Eickbush, T. H., Watson, D. K., & Moudrianakis, E. N. (1976) Cell (Cambridge, Mass.) 9, 785--792]. In the present study, we explore the nature of interactions that form and stabilize the enzyme-chromatin system by using the a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00531a008
更新日期:1982-01-19 00:00:00
abstract::Illuminating Ca2+-depleted photosystem (PS) II membranes generated two new EPR signals at g = 11 and 15 by perpendicular and parallel polarization modes, respectively. Two turnovers of the oxygen evolving center (OEC) beyond the modified S2' state are required for the appearance of these signals. The formation of the ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi972471c
更新日期:1998-03-03 00:00:00
abstract::The interaction of lipoprotein lipase (LpL) and a nonhydrolyzable phosphatidylcholine, 1,2-ditetradecyl-rac-glycero-3-phosphocholine (C14-ether-PC), has been studied by several physical methods. Analysis of the circular dichroic spectrum of LpL gave the following fractional conformation: 35% alpha-helix, 30% beta-plea...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00352a020
更新日期:1986-02-25 00:00:00
abstract::The metalloenzyme Cu/Zn-superoxide dismutase (SOD1) catalyzes the reduction of superoxide anions into molecular oxygen and hydrogen peroxide. Hydrogen peroxide can oxidize SOD1, resulting in aberrant protein conformational changes, disruption of SOD1 function, and DNA damage. Cells may have evolved mechanisms of regul...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi400613h
更新日期:2013-09-10 00:00:00
abstract::Mixed phospholipid systems of ether-linked 1,2-dihexadecylphosphatidylcholine (DHPC) and ester-linked 1,2-dipalmitoylphosphatidylcholine (DPPC) have been studied by differential scanning calorimetry and X-ray diffraction. At maximum hydration (60 wt % water), DHPC shows three reversible transitions: a main (chain melt...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00395a006
更新日期:1987-10-20 00:00:00
abstract::In addition to its superoxide dismutase (SOD) activity, Cu,Zn-superoxide dismutase (CuZnSOD) catalyzes the reductive decomposition of S-nitroso-L-glutathione (GSNO) in the presence of thiols such as L-glutathione (GSH). The GSNO-reductase activity but not the superoxide dismutase (SOD) activity of CuZnSOD is inhibited...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi061077o
更新日期:2006-10-24 00:00:00
abstract::Much interest has centered on two surface loops in the motor domain to explain the differences in enzymatic and mechanical properties of myosin isoforms. We showed that two invariant lysines at the C-terminal end of loop 2, which is part of the actin-binding interface, are required to obtain actin activation [Joel et ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi034415j
更新日期:2003-08-05 00:00:00
abstract::The FMN prosthetic group of flavocytochrome b2 or L-lactate dehydrogenase oxidizes lactate to pyruvate. The reducing equivalents are then transferred one by one, intramolecularly, to heme b2 and then to external acceptors. Substrate oxidation is thought to begin with abstraction of the substrate alpha-hydrogen as a pr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9529519
更新日期:1996-07-02 00:00:00
abstract::The structure and folding of a novel human insulin mutant, [Thr(B27) --> Pro, Pro(B28) --> Thr]insulin (PT insulin), in aqueous solution and in mixtures of water and 2,2,2-trifluoroethanol (TFE) have been studied by NMR spectroscopy. It was found that PT insulin has a highly flexible structure in pure water and is pre...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi0108150
更新日期:2001-09-04 00:00:00
abstract::The immunoglobulin E-binding protein, epsilon BP (also known as CBP35, Mac-2, L-34, and L-29), is a beta-galactoside-binding protein of approximately 30 kDa and a member of the animal lectin family termed S-type or S-Lac. Multiple biological activities have been attributed to this lectin such as mediation of IgE bindi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00186a038
更新日期:1994-05-24 00:00:00
abstract::In search of the regulation mechanisms for isoform specific myosin assembly, we have used the COOH-terminal fragments of nonmuscle myosin isoforms MIIA and MIIB (MIIA(F46) and MIIB(alpha)(F47)) as a model system. Phosphorylation by protein kinase C (PK C) or casein kinase II (CK II) within or near the nonhelical tail-...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi000347e
更新日期:2000-09-19 00:00:00
abstract::Two antisera used in the radioimmunoassay for human fibrinopeptide A (FPA) which appear to have different immunochemical specificities have been tested for cross-reactivity with fibrinogen and with three fragments of fibrinogen which contain the FPA sequence. These fragments were the three-chain, NH2-terminal disulfid...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00651a004
更新日期:1976-03-23 00:00:00
abstract::There is a significant need for new therapeutics to treat infections caused by the biodefense agent Bacillus anthracis. In pursuit of drug discovery against this organism, we have developed novel propargyl-linked inhibitors that target the essential enzyme dihydrofolate reductase (DHFR) from B. anthracis. Previously, ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi802319w
更新日期:2009-05-19 00:00:00
abstract::Modified (Arg63-Ile64 reactive-site peptide bond hydrolyzed) soybean trypsin inhibitor (Kunitz) with all reactive amino groups, except that of Ile64, protected was described in the preceding paper (Kowalski, D., and Laskowski, M., Jr. (1976), Biochemistry, preceding paper in this issue). Treatment of this inhibitor wi...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00651a022
更新日期:1976-03-23 00:00:00
abstract::The ubiquitous cyclophilins belong to peptidyl-prolyl cis/trans isomerases (PPIases; EC 5.2.1.8). They are able to catalyze the cis/trans isomerization about peptidyl-prolyl amide bonds. The mode of action of human cytosolic cyclophilin (Cyp18cy) has been studied on substrate analog tetrapeptide-4-nitroanilides contai...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00040a012
更新日期:1995-10-10 00:00:00
abstract::Ribosomal protein E-L30 unfolds reversibly at pH values between 7.0 and 4.5. Unfolding of the protein involves a fast and a slow equilibrium, which depend on the degree of protonation of His19 and His33. Both the fast equilibrium between protonated and deprotonated histidines and the slow equilibrium between folded an...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00391a050
更新日期:1987-08-25 00:00:00
abstract::The Raman spectra of the nonbridging V--O bonds in the myosin S1.MgADP.Vi complex, often believed to be a transition-state analogue for the phosphotransfer reaction catalyzed by myosin, and in a vanadate solution model compound have been obtained using Raman difference spectroscopic techniques. A symmetric/asymmetric ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi980556n
更新日期:1998-08-04 00:00:00
abstract::Calcium trapped within sonicated and resealed bovine rod outer segment disks is released upon light exposure with a stoichiometry of 0.75 +/- 0.05 calcium for each rhodopsin bleached. The amount of calcium liberated is proportional to the amount of bleaching in the range of 20 to 100% bleaching and is relatively insen...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00626a025
更新日期:1977-04-05 00:00:00
abstract::Polynucleosomes with poly(dG-m5dC).poly(dG-m5dC) have been reconstituted, and well-defined nucleosome core particles from these have been prepared. Upon addition of MgCl2 to the levels used to induce the B to Z transition in this highly methylated DNA, significant changes in the circular dichroism spectrum are observe...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00392a003
更新日期:1987-09-08 00:00:00