Abstract:
:Alzheimer's disease is a debilitating neurodegenerative disorder whose pathology has been linked to the aggregation and deposition of the amyloid β-peptide (Aβ) in neural tissue. A truly effective therapeutic agent remains elusive, and attention has recently turned to the use of natural products as effective antiaggregation compounds, directly targeting Aβ. Although a wealth of in vitro and in vivo evidence suggests these compounds or their derivatives might be beneficial, a detailed understanding of the mechanism by which they act remains largely unknown. Using atomistic, explicit-solvent molecular dynamics simulations, we have investigated the association of the flavonoid morin with Aβ monomers and dimers. Through 90 simulations totaling 23.65 μs, we found that treatment of Aβ peptides with morin largely does not affect secondary structure content, unless a large molar excess of morin is present. However, in simulations of Aβ monomers and dimers, morin affected the tertiary and quaternary structure of Aβ, even at low concentrations that have been used experimentally. Thus it appears that despite the inability of morin to fully block Aβ aggregation or β-strand formation, we observe structures with altered tertiary and quaternary interactions, which may represent "off-pathway" aggregates that have been proposed previously. The simulations presented here add important new details to the mechanism of these processes.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Lemkul JA,Bevan DRdoi
10.1021/bi300113xsubject
Has Abstractpub_date
2012-07-31 00:00:00pages
5990-6009issue
30eissn
0006-2960issn
1520-4995journal_volume
51pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract::The guanidine hydrochloride- (GuHCl-) induced unfolding and refolding of a recombinant domain of bovine microsomal cytochrome b(5) containing the first 104 amino acid residues has been characterized by both transient and equilibrium spectrophotometric methods. The soluble domain is reversibly unfolded and the equilibr...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi991413j
更新日期:1999-10-26 00:00:00
abstract::The influence of structural alterations to the estradiol-17 beta (E2) molecule on the induction of pS2 and Cathepsin D (Cath D) mRNAs has been examined by Northern analysis of RNA extracted from MCF-7 cells. Exposure of cultures to estratriene did not affect the level of expression of these estrogen-responsive genes. ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00078a028
更新日期:1993-07-13 00:00:00
abstract::Serine transacetylase from Salmonella typhimurium was purified to near homogeneity. A complete initial velocity study in both reaction directions suggests that the enzyme catalyzes the conversion of acetyl CoA and L-serine to O-acetyl-L-serine (OAS) and coenzyme A (CoASH) by a ping pong bi bi kinetic mechanism. Initia...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00175a040
更新日期:1994-03-08 00:00:00
abstract::The structure of octylcarbamoyl-alpha-chymotrypsin to a resolution of 3.0 A is described. The n-octyl side chain of the active site directed irreversible inactivator octyl isocyanate is bound exclusively in the hydrophobic substrate binding pocket. The n-octyl isocyanate forms a planar urethane bond with the Ser-195 O...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00694a008
更新日期:1975-11-18 00:00:00
abstract::The Ndi1 enzyme found in the mitochondrial membrane of Saccharomyces cerevisiae is an NDH-2-type alternative NADH-quinone oxidoreductase. As Ndi1 is expected to be a possible remedy for complex I defects of mammalian mitochondria, a detailed biochemical characterization of the enzyme is needed. To identify the ubiquin...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi100005j
更新日期:2010-04-06 00:00:00
abstract::Signal transducer and activator of transcription factors (STATs) are proteins that can translocate into the nucleus, bind DNA, and activate gene transcription. STAT proteins play a crucial role in cell proliferation, apoptosis, and differentiation. The prevalent view is that STAT proteins are able to form dimers and b...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi501529x
更新日期:2015-09-08 00:00:00
abstract::Picosecond absorption spectroscopy has been used to investigate energy-transfer dynamics within the LH1 and LH2 light-harvesting complexes of three mutants of Rhodobacter sphaeroides. We demonstrate that both complexes are inhomogeneous; each contains a specialized pigment pool which absorbs maximally at a longer wave...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00465a008
更新日期:1990-04-03 00:00:00
abstract::Nanosecond to millisecond conformational fluctuations of Zn-substituted cytochrome c (ZnCytc) have been studied by the time-resolved transient hole-burning method. The investigation of low-temperature dynamics has been made on the ZnCytc solution sample in a water-glycerol mixture. The conformational fluctuations in t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi981568b
更新日期:1999-02-09 00:00:00
abstract::The zinc-dependent metallo-beta-lactamases are a group of bacterial enzymes that pose a threat to the future efficacy of present-day antibiotics. Their mechanism is poorly understood, and there are no clinically useful inhibitors. While most members of the group contain two tightly bound zinc ions in their active site...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi047709t
更新日期:2005-03-29 00:00:00
abstract::Thermal and chemical modification of protein structures is known to affect their interfacial activity. We have looked in detail at the effect of heating on the structure and subsequently the surface properties of LTP1, a nonspecific lipid transfer protein from barley, both in the presence and in the absence of its lip...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi901328f
更新日期:2009-12-29 00:00:00
abstract::Supported phospholipid bilayers prepared by Langmuir-Blodgett techniques were introduced recently as a new model membrane system [Tamm, L.K., & McConnell, H.M. (1985) Biophys. J. 47, 105-113]. Here, supported bilayers are applied to study the lateral diffusion and lateral distribution of membrane-bound monoclonal anti...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00405a009
更新日期:1988-03-08 00:00:00
abstract::There is increasing evidence that a class of cell membrane glycolipids, gangliosides, can mediate the fibrillogenesis and toxicity of Alzheimer's disease amyloid-beta peptide (Abeta). Using lipid monolayers and vesicles as model membranes, we measured the insertion of Abeta into 1,2-dipalmitoyl-sn-glycero-3-phosphocho...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi062177x
更新日期:2007-02-20 00:00:00
abstract::Solvent reorganization can contribute significantly to the energetics of protein-protein interactions. However, our knowledge of the magnitude of the energetic contribution is limited, in part, by a dearth of quantitative experimental measurements. The biotin repressor forms a homodimer as a prerequisite to DNA bindin...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi400952m
更新日期:2013-09-24 00:00:00
abstract::Endothelium-derived epoxyeicosatrienoic acids (EETs) relax vascular smooth muscle by activating potassium channels and causing membrane hyperpolarization. Recent evidence suggests that EETs act via a membrane binding site or receptor. To further characterize this binding site or receptor, we synthesized 20-iodo-14,15-...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi102070w
更新日期:2011-05-10 00:00:00
abstract::Kynureninase is a pyridoxal 5'-phosphate-dependent enzyme that catalyzes the hydrolytic cleavage of l-kynurenine to give l-alanine and anthranilic acid. beta-Benzoyl-l-alanine, the analogue of l-kynurenine lacking the aromatic amino group, was shown to a good substrate for kynureninase from Pseudomonas fluorescens, an...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi100955b
更新日期:2010-09-14 00:00:00
abstract::In this paper the interaction of cytoplasmic CopZ and the N-terminal domain of the CopA ATPase from Bacillus subtilis has been studied by NMR through (15)N-(1)H HSQC experiments in order to understand the role of the two proteins in the whole copper trafficking mechanism of the bacteria. It appears that the two protei...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi027096p
更新日期:2003-02-25 00:00:00
abstract::The complete sequence of histone 2B of Drosophila has been determined by using an improved Beckman sequenator. Comparing these data with those previously published by other investigators on the histone 2B of calf [Iwai, K., Hayashi, H., & Ishikawa, K. (1972) J. Biochem. (Tokyo) 72, 357--367], trout [Koostra, A., & Bai...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00592a025
更新日期:1979-12-11 00:00:00
abstract::Proteins from thermophiles possess high thermostability. The stabilization mechanisms differ between archaeal and bacterial proteins, whereby archaeal proteins are mainly stabilized via hydrophobic interactions and bacterial proteins by ion pairs. High stability is an important factor in promoting protein evolution, b...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi400652c
更新日期:2013-07-16 00:00:00
abstract::Mutations in human copper-zinc superoxide dismutase (SOD1) cause an inherited form of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS). Here, we present structures of the pathogenic SOD1 variants D124V and H80R, both of which demonstrate compromised zinc-binding sites. The disruption of the zinc...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi100314n
更新日期:2010-07-13 00:00:00
abstract::The cell-surface component (alpha) which binds monomeric immunoglobulin E with high affinity is associated with a second polypeptide (beta) in the plasma membrane. The latter component tends to dissociate during purification of the alpha chain from detergent extracts of cells, even at neutral pHs and physiological ion...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00269a047
更新日期:1982-12-21 00:00:00
abstract::The assignment of the 1H, 15N, 13CO, and 13C resonances of recombinant human interleukin-4 (IL-4), a protein of 133 residues and molecular mass of 15.4 kDa, is presented based on a series of 11 three-dimensional (3D) double- and triple-resonance heteronuclear NMR experiments. These studies employ uniformly labeled 15N...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00132a026
更新日期:1992-05-05 00:00:00
abstract::Troponin T (TnT) is an essential element in the thin filament-based regulatory system of striated muscle. Alternative mRNA splicing generates multiple TnT isoforms with primary structural differences in the NH2-terminal region. The functional significance of this hypervariable NH2-terminal domain and the developmental...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi9812322
更新日期:1998-10-13 00:00:00
abstract::The mechanism by which some hydrophobic molecules such as steroids and free fatty acids (FFA) act as noncompetitive inhibitors of the nicotinic acetylcholine receptor (AChR) is still not known. In the present work, we employ Förster resonance energy transfer (FRET) between the intrinsic fluorescence of membrane-bound ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi061388z
更新日期:2007-03-20 00:00:00
abstract::The DNA binding domain of the yeast transcription factor Mbp1 is a winged helix-turn-helix structure, with an extended DNA binding site involving C-terminal "tail" residues. The thermodynamics of the interaction of the DNA binding domain with its target DNA sequence have been determined using fluorescence anisotropy a...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi702339q
更新日期:2008-06-17 00:00:00
abstract::A complex derived from chromatin containing one molecule of each of histones H2A, H2B, H3, and H4, termed core protein, was studied by 13C and 1H nuclear magnetic resonance. 13C line widths, when analyzed and compared with those of native and thermally unfolded representative globular proteins, showed that regions of ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00632a008
更新日期:1977-06-28 00:00:00
abstract::The microtubule-associated protein tau, in a hyperphosphorylated form, aggregates into insoluble paired-helical filaments (PHFs) in Alzheimer's disease (AD) and other tauopathies. In AD, there is approximately 8 mol of phosphate per mole of tau distributed among approximately 30 PHF phosphorylation sites as compared t...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi900602h
更新日期:2009-06-30 00:00:00
abstract::The highly conserved nature and tissue specificity of the seven vertebrate beta-tubulin isotypes provide circumstantial evidence that functional differences among isotypes may exist in vivo. Compelling evidence from studies of bovine brain beta-isotypes indicated significant conformational and functional differences i...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi972763d
更新日期:1998-03-31 00:00:00
abstract::The crystal structure of the heme-copper oxidases suggested a putative channel of oxygen entry into the heme-copper site of O(2) reduction. Changing a conserved valine near this center in cytochrome bo(3) of Escherichia coli to isoleucine caused a significant increase in the apparent K(M) for oxygen with little or no ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi000123w
更新日期:2000-05-30 00:00:00
abstract::A new strategy for the assignment of nonexchangeable proton resonances in oligonucleotide duplexes is presented and used to interpret the spectra of the oligonucleotide helix d(CpGpCpGpCpG) X d(CpGpCpGpCpG) in low salt (B form). This procedure is based on the use of sequential homodecoupling (1D) or COSY (2D) for the ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi00291a020
更新日期:1983-10-25 00:00:00
abstract::Replication protein A (RPA) is a heterotrimeric protein that is required for DNA replication and most DNA repair pathways. RPA has previously been shown to play a role in recognizing and binding damaged DNA during nucleotide excision repair (NER). RPA has also been suggested to play a role in psoralen DNA interstrand ...
journal_title:Biochemistry
pub_type: 杂志文章
doi:10.1021/bi800460d
更新日期:2008-09-23 00:00:00