scholarly journals The Role of Helix 1 Aspartates and Salt Bridges in the Stability and Conversion of Prion Protein

2003 ◽  
Vol 278 (14) ◽  
pp. 12522-12529 ◽  
Author(s):  
Jonathan O. Speare ◽  
Thomas S. Rush ◽  
Marshall E. Bloom ◽  
Byron Caughey
Keyword(s):  
Prion Protein ◽  
Salt Bridges ◽  
The Stability

scholarly journals Electrostatics in the stability and misfolding of the prion protein: salt bridges, self energy, and solvationThis paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular & Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process.

2010 ◽  
Vol 88 (2) ◽  
pp. 371-381 ◽  
Author(s):  
Will C. Guest ◽  
Neil R. Cashman ◽  
Steven S. Plotkin
Keyword(s):  
Prion Protein ◽  
Electrostatic Potential ◽  
Peer Review Process ◽  
Salt Bridge ◽  
Salt Bridges ◽  
Self Energy ◽  
Low Dielectric ◽  
The Stability ◽  
Α Helix ◽  
Electrostatic Potential Energy

Using a recently developed mesoscopic theory of protein dielectrics, we have calculated the salt bridge energies, total residue electrostatic potential energies, and transfer energies into a low dielectric amyloid-like phase for 12 species and mutants of the prion protein. Salt bridges and self energies play key roles in stabilizing secondary and tertiary structural elements of the prion protein. The total electrostatic potential energy of each residue was found to be invariably stabilizing. Residues frequently found to be mutated in familial prion disease were among those with the largest electrostatic energies. The large barrier to charged group desolvation imposes regional constraints on involvement of the prion protein in an amyloid aggregate, resulting in an electrostatic amyloid recruitment profile that favours regions of sequence between α helix 1 and β strand 2, the middles of helices 2 and 3, and the region N-terminal to α helix 1. We found that the stabilization due to salt bridges is minimal among the proteins studied for disease-susceptible human mutants of prion protein.

Investigation on salt bridge interactions of mammalian prion proteins by molecular dynamics simulation / Memeli prion proteinlerinin moleküler dinamik simulasyon ile tuz köprüleri etkileşimlerinin araştırılması

2016 ◽  
Vol 41 (3) ◽  
Author(s):  
Xiliang Chen ◽  
Xin Chen ◽  
Yafang Liu
Keyword(s):  
Molecular Dynamics ◽  
Prion Protein ◽  
Electrostatic Interactions ◽  
Prion Proteins ◽  
Salt Bridge ◽  
Dynamics Simulation ◽  
Salt Bridges ◽  
Tertiary Structures ◽  
Local Structures ◽  
The Stability

AbstractObjective: Salt bridge interaction is one of the most important electrostatic interactions to stabilize the secondary and tertiary structures of protein. To obtain more insight into the molecular basis of prion proteins, the salt bridge networks in two animal prion proteins are studied in this work.Methods: Molecular dynamics (MD) and Flow MD (FMD) simulations are employed to investigate the salt bridges interactions of rabbit prion protein (rPrPc), Syrian hamster prion protein (syPrPc) and the variants of the two prion proteins.Results: The dynamic behaviors of salt bridges are characterized, and the relation between salt bridge interactions and local structures are also discussed. The type of salt bridges in the two prion proteins is divided into the helixloop, intra-helix and inter-helix salt bridges. It is found that the helix-loop salt bridges is more important for the stability of prion proteins than the other two kinds of slat bridge.Conclusion: The Asp201-Arg155 (rS1), Asp177-Arg163 (rS3) and Asp178-Arg164 (syS1) are the important salt bridges to stabilize the structures of rPrPc and syPrPc, respectively. The structural stability is partly depended on the number of helix-loop salt bridge.

Insights into stabilizing interactions in the distorted domain-swapped dimer ofSalmonella typhimuriumsurvival protein

2015 ◽  
Vol 71 (9) ◽  
pp. 1812-1823 ◽  
Author(s):  
Yamuna Kalyani Mathiharan ◽  
H. S. Savithri ◽  
M. R. N. Murthy
Keyword(s):  
Hydrogen Bond ◽  
Catalytic Activity ◽  
Salt Bridge ◽  
Salt Bridges ◽  
X Ray ◽  
Dimeric Interface ◽  
Distorted Structure ◽  
Dimeric Protein ◽  
The Stability

The survival protein SurE fromSalmonella typhimurium(StSurE) is a dimeric protein that functions as a phosphatase. SurE dimers are formed by the swapping of a loop with a pair of β-strands and a C-terminal helix between two protomers. In a previous study, the Asp230 and His234 residues were mutated to Ala to abolish a hydrogen bond that was thought to be crucial for C-terminal helix swapping. These mutations led to functionally inactive and distorted dimers in which the two protomers were related by a rotation of 167°. New salt bridges involving Glu112 were observed in the dimeric interface of the H234A and D230A/H234A mutants. To explore the role of these salt bridges in the stability of the distorted structure, E112A, E112A/D230A, E112A/H234A, E112A/D230A/H234A, R179L/H180A/H234A and E112A/R179L/H180A/H234A mutants were constructed. X-ray crystal structures of the E112A, E112A/H234A and E112A/D230A mutants could be determined. The dimeric structures of the E112A and E112A/H234A mutants were similar to that of native SurE, while the E112A/D230A mutant had a residual rotation of 11° between theBchains upon superposition of theAchains of the mutant and native dimers. The native dimeric structure was nearly restored in the E112A/H234A mutant, suggesting that the new salt bridge observed in the H234A and D230A/H234A mutants was indeed responsible for the stability of their distorted structures. Catalytic activity was also restored in these mutants, implying that appropriate dimeric organization is necessary for the activity of SurE.

scholarly journals Intrinsic basis of thermostability of prolyl oligopeptidase from Pyrococcus furiosus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sahini Banerjee ◽  
Parth Sarthi Sen Gupta ◽  
Rifat Nawaz Ul Islam ◽  
Amal Kumar Bandyopadhyay
Keyword(s):  
Pyrococcus Furiosus ◽  
Intrinsic Property ◽  
Salt Bridge ◽  
Primary Role ◽  
Salt Bridges ◽  
Energy Contribution ◽  
Desolvation Energy ◽  
The Stability ◽  
Intrinsic Basis

AbstractSalt-bridges play a key role in the thermostability of proteins adapted in stress environments whose intrinsic basis remains to be understood. We find that the higher hydrophilicity of PfP than that of HuP is due to the charged but not the polar residues. The primary role of these residues is to enhance the salt-bridges and their ME. Unlike HuP, PfP has made many changes in its intrinsic property to strengthen the salt-bridge. First, the desolvation energy is reduced by directing the salt-bridge towards the surface. Second, it has made bridge-energy more favorable by recruiting energetically advantageous partners with high helix-propensity among the six possible salt-bridge pairs. Third, ME-residues that perform intricate interactions have increased their energy contribution by making major changes in their binary properties. The use of salt-bridge partners as ME-residues, and ME-residues' overlapping usage, predominant in helices, and energetically favorable substitution are some of the favorable features of PfP compared to HuP. These changes in PfP reduce the unfavorable, increase the favorable ME-energy. Thus, the per salt-bridge stability of PfP is greater than that of HuP. Further, unfavorable target ME-residues can be identified whose mutation can increase the stability of salt-bridge. The study applies to other similar systems.

A Statistical Study of Process Variables to Optimize a High Speed Curtain Coater: Part I

TAPPI Journal ◽  
2009 ◽  
Vol 8 (1) ◽  
pp. 20-26 ◽  
Author(s):  
PEEYUSH TRIPATHI ◽  
MARGARET JOYCE ◽  
PAUL D. FLEMING ◽  
MASAHIRO SUGIHARA
Keyword(s):  
Boundary Layer ◽  
Experimental Design ◽  
High Speed ◽  
Statistical Study ◽  
Process Variables ◽  
High Speeds ◽  
The Stability ◽  
Air Removal ◽  
Removal System

Using an experimental design approach, researchers altered process parameters and material prop-erties to stabilize the curtain of a pilot curtain coater at high speeds. Part I of this paper identifies the four significant variables that influence curtain stability. The boundary layer air removal system was critical to the stability of the curtain and base sheet roughness was found to be very important. A shear thinning coating rheology and higher curtain heights improved the curtain stability at high speeds. The sizing of the base sheet affected coverage and cur-tain stability because of its effect on base sheet wettability. The role of surfactant was inconclusive. Part II of this paper will report on further optimization of curtain stability with these four variables using a D-optimal partial-facto-rial design.

The Role of Hydrophobicity in the Stability and pH-Switchability of (RXDX)4 and Coumarin-RXDX Conjugate β-Sheets

2020 ◽  
Author(s):  
Ryan Weber ◽  
Martin McCullagh
Keyword(s):  
Biological Imaging ◽  
Ph Sensing ◽  
Hydrophobic Residue ◽  
Ideal Candidate ◽  
Self Assembling ◽  
Sensing Applications ◽  
Β Sheets ◽  
The Stability ◽  
Dynamics Simulations

<p>pH-switchable, self-assembling materials are of interest in biological imaging and sensing applications. Here we propose that combining the pH-switchability of RXDX (X=Ala, Val, Leu, Ile, Phe) peptides and the optical properties of coumarin creates an ideal candidate for these materials. This suggestion is tested with a thorough set of all-atom molecular dynamics simulations. We first investigate the dependence of pH-switchabiliy on the identity of the hydrophobic residue, X, in the bare (RXDX)<sub>4</sub> systems. Increasing the hydrophobicity stabilizes the fiber which, in turn, reduces the pH-switchabilty of the system. This behavior is found to be somewhat transferable to systems in which a single hydrophobic residue is replaced with a coumarin containing amino acid. In this case, conjugates with X=Ala are found to be unstable and both pHs while conjugates with X=Val, Leu, Ile and Phe are found to form stable β-sheets at least at neutral pH. The (RFDF)<sub>4</sub>-coumarin conjugate is found to have the largest relative entropy value of 0.884 +/- 0.001 between neutral and acidic coumarin ordering distributions. Thus, we posit that coumarin-(RFDF)<sub>4</sub> containing peptide sequences are ideal candidates for pH-sensing bioelectronic materials.</p>

Metal-Metal Cooperative Bond Activation by Heterobimetallic Alkyl, Aryl, and Acetylide PtII/CuI Complexes

2020 ◽  
Author(s):  
Shubham Deolka ◽  
Orestes Rivada Wheelaghan ◽  
Sandra Aristizábal ◽  
Robert Fayzullin ◽  
Shrinwantu Pal ◽  
...  
Keyword(s):  
Alkyl Group ◽  
Bond Activation ◽  
Bond Cleavage ◽  
Terminal Alkyne ◽  
Alkyl Aryl ◽  
Metal Metal ◽  
The Stability ◽  
Selective Formation ◽  
Organoplatinum Compounds

We report selective formation of heterobimetallic PtII/CuI complexes that demonstrate how facile bond activation processes can be achieved by altering reactivity of common organoplatinum compounds through their interaction with another metal center. The interaction of the Cu center with Pt center and with a Pt-bound alkyl group increases the stability of PtMe2 towards undesired rollover cyclometalation. The presence of the CuI center also enables facile transmetalation from electron-deficient tetraarylborate [B(ArF)4]- anion and mild C-H bond cleavage of a terminal alkyne, which was not observed in the absence of an electrophilic Cu center. The DFT study indicates that the role of Cu center acts as a binding site for alkyne substrate, while activating its terminal C-H bond.

LANDSLIDE RISK MANAGEMENT IN THE COASTAL ZONE OF THE KUIBYSHEV RESERVOIR DUE THE DESIGN OF HIGH-SPEED LINE "MOSCOW-KAZAN"

2017 ◽  
Author(s):  
Nikolai Petrov ◽  
Nikolai Petrov ◽  
Inna Nikonorova ◽  
Inna Nikonorova ◽  
Vladimir Mashin ◽  
...  
Keyword(s):  
High Speed ◽  
Computational Models ◽  
Stable State ◽  
Landslide Risk ◽  
Kuibyshev Reservoir ◽  
Stepped Surface ◽  
The Stability ◽  
Landslide Slope ◽  
The Village

High-speed railway "Moscow-Kazan" by the draft crosses the Volga (Kuibyshev reservoir) in Chuvashia region 500 m below the village of New Kushnikovo. The crossing plot is a right-bank landslide slope with a stepped surface. Its height is 80 m; the slope steepness -15-16o. The authors should assess the risk of landslides and recommend anti-landslide measures to ensure the safety of the future bridge. For this landslide factors have been analyzed, slope stability assessment has been performed and recommendations have been suggested. The role of the following factors have been analyzed: 1) hydrologic - erosion and abrasion reservoir and runoff role; 2) lithologyc (the presence of Urzhum and Northern Dvina horizons of plastically deformable rocks, displacement areas); 3) hydrogeological (the role of perched, ground and interstratal water); 4) geomorphological (presence of the elemental composition of sliding systems and their structure in the relief); 5) exogeodynamic (cycles and stages of landslide systems development, mechanisms and relationship between landslide tiers of different generations and blocks contained in tiers). As a result 6-7 computational models at each of the three engineering-geological sections were made. The stability was evaluated by the method “of the leaning slope”. It is proved that the slope is in a very stable state and requires the following measures: 1) unloading (truncation) of active heads blocks of landslide tiers) and the edge of the plateau, 2) regulation of the surface and groundwater flow, 3) concrete dam, if necessary.

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