Spatial Separation of β-Sheet Domains of β-Amyloid:  Disruption of Each β-Sheet byN-Methyl Amino Acids†

Biochemistry ◽  
2006 ◽  
Vol 45 (31) ◽  
pp. 9485-9495 ◽  
Author(s):  
Kimberly L. Sciarretta ◽  
Adrienne Boire ◽  
David J. Gordon ◽  
Stephen C. Meredith
Keyword(s):  
Amino Acids ◽  
Spatial Separation ◽  
Β Amyloid ◽  
Β Sheet

scholarly journals TraA and its N-terminal relaxase domain of the Gram-positive plasmid pIP501 show specific oriT binding and behave as dimers in solution

2005 ◽  
Vol 387 (2) ◽  
pp. 401-409 ◽  
Author(s):  
Jolanta KOPEC ◽  
Alexander BERGMANN ◽  
Gerhard FRITZ ◽  
Elisabeth GROHMANN ◽  
Walter KELLER
Keyword(s):  
Amino Acids ◽  
Broad Host Range ◽  
Mobility Shift ◽  
Gram Positive ◽  
Nick Site ◽  
Α Helix ◽  
Electrophoretic Mobility Shift Assays ◽  
Dna Complex ◽  
Β Sheet

TraA is the DNA relaxase encoded by the broad-host-range Grampositive plasmid pIP501. It is the second relaxase to be characterized from plasmids originating from Gram-positive organisms. Full-length TraA (654 amino acids) and the N-terminal domain (246 amino acids), termed TraAN246, were expressed as 6×His-tagged fusions and purified. Small-angle X-ray scattering and chemical cross-linking proved that TraAN246 and TraA form dimers in solution. Both proteins revealed oriTpIP501 (origin of transfer of pIP501) cleavage activity on supercoiled plasmid DNA in vitro. oriT binding was demonstrated by electrophoretic mobility shift assays. Radiolabelled oligonucleotides covering different parts of oriTpIP501 were subjected to binding with TraA and TraAN246. The KD of the protein–DNA complex encompassing the inverted repeat, the nick site and an additional 7 bases was found to be 55 nM for TraA and 26 nM for TraAN246. The unfolding of both protein constructs was monitored by measuring the change in the CD signal at 220 nm upon temperature change. The unfolding transition of both proteins occurred at approx. 42 °C. CD spectra measured at 20 °C showed 30% α-helix and 13% β-sheet for TraA, and 27% α-helix and 18% β-sheet content for the truncated protein. Upon DNA binding, an enhanced secondary structure content and increased thermal stability were observed for the TraAN246 protein, suggesting an induced-fit mechanism for the formation of the specific relaxase–oriT complex.

On the Possible Spatial Structures of the β – Amyloid.

2022 ◽  
Vol 7 (1) ◽  
pp. 0-0
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Spatial Structure ◽  
Spatial Models ◽  
Globular Proteins ◽  
Spatial Structures ◽  
Higher Dimensional ◽  
Protein Molecules ◽  
Β Amyloid ◽  
First Time

Spatial models of the β - structures of protein molecules, forming layers of amino acids, in principle, of unlimited length for both antiparallel and parallel conformation have been constructed. It is shown that the simplified flat Pauling models do not reflect the spatial structure of these layers. Using the recently developed theory of higher-dimensional polytopic prismahedrons, models of the volumetric filling of space with amino acid molecules are constructed. The constructed models for the first time mathematically describe the native structures of globular proteins.

Designed Amino Acids That Induce β-Sheet Folding and β-Sheet Interactions in Peptides

2001 ◽  
pp. 572-574
Author(s):  
James S. Nowick ◽  
Kit S. Lam ◽  
Chris M. Gothard ◽  
Jeffrey K. Huon ◽  
William E. Kemnitzer ◽  
...  
Keyword(s):  
Amino Acids ◽  
Β Sheet

The molecular mechanism of fullerene-inhibited aggregation of Alzheimer's β-amyloid peptide fragment

Nanoscale ◽  
2014 ◽  
Vol 6 (16) ◽  
pp. 9752-9762 ◽  
Author(s):  
Luogang Xie ◽  
Yin Luo ◽  
Dongdong Lin ◽  
Wenhui Xi ◽  
Xinju Yang ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Inhibitory Effect ◽  
Amyloid Peptide ◽  
Peptide Fragment ◽  
Experiment Study ◽  
Simulation And Experiment ◽  
Β Amyloid ◽  
Combined Simulation ◽  
Β Amyloid Peptide ◽  
Β Sheet

A combined simulation and experiment study demonstrates that fullerenes inhibit the β-sheet formation of Aβ(16–22) and fullerene hexagonal rings play a significant role on the inhibitory effect.

The Bβ-sheet in the PAI-1 Molecule Plays an Important Role for Its Stability

2000 ◽  
Vol 83 (06) ◽  
pp. 896-901 ◽  
Author(s):  
Guang-Chao Sui ◽  
Björn Wiman
Keyword(s):  
Amino Acids ◽  
Half Life ◽  
Ph Dependence ◽  
The Other ◽  
Wild Type ◽  
E Coli ◽  
Reactive Center ◽  
The Stability ◽  
Β Sheet ◽  
Pai 1

SummaryWe have investigated the B β-sheet in PAI-1 regarding its role for the stability of the molecule. The residues from His219 to Tyr241 (except for Gly230 and Pro240), covering the s2B and s3B strands, and in addition His185 and His190 were substituted by amino acids with opposite properties. The 23 generated single-site changed mutants and also wild type PAI-1 (wtPAI-1) were expressed in E. coli. Subsequently they were purified by heparin-Sepharose and anhydrotrypsin agarose affinity chromatographies. The stability of the purified PAI-1 variants was analyzed at 37° C and at different pHs (5.5, 6.5 or 7.5). At pH 7.5 and 37° C, single substitutions of the residues in the central portions of both strands 2 and 3 in the B β-sheet (Ile223 to Leu226 on s2B and Met235 to Ile237 on s3B), caused a significant decrease in stability, yielding half-lives of about 10–25% as compared to wtPAI-1. On the other hand, mutations at both sides of the central portion of the B β-sheet (Tyr221, Asp222, Tyr228 and Thr232) frequently resulted in an increased PAI-1 stability (up to 7-fold). While wtPAI-1 exhibited prolonged half-lives at pH 6.5 and 5.5, the PAI-1 variant Y228S was more stable at neutral pH (half-life of 9.6 h at pH 7.5) as compared to its half-life at pH 5.5 (1.1 h). One of the 4 modified histidine residues (His229) resulted in a variant with a clearly affected stability as a function of pH, suggesting that it may, at least in part, be of importance for the pH dependence of the PAI-1 stability. Thus, our data demonstrate that the B β-sheet is of great importance for the stability of the molecule. Modifications in this part causes decreased or increased stability in a certain pattern, suggesting effects on the insertion rate of the reactive center loop into the A β-sheet of the molecule.

scholarly journals Aza-Amino Acids Disrupt β-Sheet Secondary Structures

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1919 ◽  
Author(s):  
Michael A. McMechen ◽  
Evan L. Willis ◽  
Preston C. Gourville ◽  
Caroline Proulx
Keyword(s):  
Amino Acids ◽  
Self Assembly ◽  
Secondary Structures ◽  
Model Peptide ◽  
Amino Acid Incorporation ◽  
Acid Incorporation ◽  
Conformational Constraints ◽  
Bonding Properties ◽  
Β Sheet ◽  
Hairpin Formation

Cα to N substitution in aza-amino acids imposes local conformational constraints, changes in hydrogen bonding properties, and leads to adaptive chirality at the nitrogen atom. These properties can be exploited in mimicry and stabilization of peptide secondary structures and self-assembly. Here, the effect of a single aza-amino acid incorporation located in the upper β-strand at a hydrogen-bonded (HB) site of a β-hairpin model peptide (H-Arg-Tyr-Val-Glu-Val-d-Pro-Gly-Orn-Lys-Ile-Leu-Gln-NH2) is reported. Specifically, analogs in which valine3 was substituted for aza-valine3 or aza-glycine3 were synthesized, and their β-hairpin stabilities were examined using Nuclear Magnetic Resonance (NMR) spectroscopy. The azapeptide analogs were found to destabilize β-hairpin formation compared to the parent peptide. The aza-valine3 residue was more disruptive of β-hairpin geometry than its aza-glycine3 counterpart.

scholarly journals ROSETTA-informed design of structurally stabilized cyclic anti-amyloid peptides

2019 ◽  
Vol 32 (2) ◽  
pp. 47-57 ◽  
Author(s):  
Chandler B Est ◽  
Parth Mangrolia ◽  
Regina M Murphy
Keyword(s):  
Amyloid Fibril ◽  
Cyclic Peptide ◽  
Bond Formation ◽  
Amyloid Peptides ◽  
Linear Peptide ◽  
Toxic Species ◽  
Disulfide Linkages ◽  
Amyloid Oligomers ◽  
Β Amyloid ◽  
Β Sheet

Abstract β-amyloid oligomers are thought to be the most toxic species formed en route to fibril deposition in Alzheimer’s disease. Transthyretin is a natural sequestering agent of β-amyloid oligomers: the binding site to β-amyloid has been traced to strands G/H of the inner β-sheet of transthyretin. A linear peptide, with the same primary sequence as the β-amyloid binding domain on transthyretin, was moderately effective at inhibiting β-amyloid fibril growth. Insertion of a β-turn template and cyclization greatly increased stability against proteolysis and improved efficacy as an amyloid inhibitor. However, the cyclic peptide still contained a significant amount of disorder. Using the Simple Cyclic Peptide Application within ROSETTA as an in silico predictor of cyclic peptide conformation and stability, we investigated putative structural enhancements, including stabilization by disulfide linkages and insertion of a second β-turn template. Several candidates were synthesized and tested for secondary structure and ability to inhibit β-amyloid aggregation. The results demonstrate that cyclization, β-sheet structure and conformational homogeneity are all preferable design features, whereas disulfide bond formation across the two β-strands is not preferable.

Reaction between the Pt(II)-complexes and the amino acids of the β-amyloid peptide

2017 ◽  
Vol 667 ◽  
pp. 4-8 ◽  
Author(s):  
Willian T.G. Novato ◽  
Pedro Henrique F. Stroppa ◽  
Adilson D. Da Silva ◽  
Naiara P. Botezine ◽  
Flávia C. Machado ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amyloid Peptide ◽  
Β Amyloid ◽  
Β Amyloid Peptide
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