scholarly journals MD Simulations on the Influence of Disease-Related Amino Acid Mutations in the Human Prion Protein

2003 ◽  
Vol 3 ◽  
pp. 86-95 ◽  
Author(s):  
Kholmirzo Kholmurodov ◽  
Yoshinori Hirano ◽  
Toshikazu Ebisuzaki
Keyword(s):  
Amino Acid ◽  
Prion Protein ◽  
Md Simulations ◽  
Human Prion Protein ◽  
Amino Acid Mutations ◽  
Related Amino Acid

scholarly journals Mutation in DsbA signal sequence hampers the SRP mechanism: A new strategy to combat virulence factor

2018 ◽  
Author(s):  
Faiza Gul Durrani ◽  
Roquyya Gul ◽  
Muhammad Usman Mirza ◽  
Naheed Nazly Kaderbhai ◽  
Mahjabeen Saleem ◽  
...  
Keyword(s):  
Amino Acid ◽  
Virulence Factor ◽  
Particle System ◽  
Signal Sequence ◽  
Binding Free Energy ◽  
Signal Recognition Particle ◽  
Md Simulations ◽  
Free Energy Calculations ◽  
New Strategy ◽  
Amino Acid Mutations

AbstractDisulphide bond (Dsb) protein, characterized as an important virulence factor in gram negative bacteria. In this study, amino acid mutations in DsbA signal sequence (ss) and its effect on translocation of recombinant Ovine growth hormone (rOGH) was observed. Eight constructs were designed on the basis of increased hydrophobicity and showed that hydrophobicity and specificity of amino acid plays a crucial role in translocation of rOGH. Two DsbAss with the same hydropathy (1.539), one had alteration at -13 and second at -11 position; alanine (Ala) to isoleucine respectively were designed. The former DsbAss translocated rOGH from membrane to cytoplasmic fraction in E. coli as confirmed by SDS-PAGE, Western blot and molecular modelling analysis. MD simulations and binding free energy calculations evidenced that, altering Ala changed the orientation of signal peptide in the Ffh-M domain binding groove and hampered the process of translocation while change at position -11 pointed it outward. We hypothesize, amino acid and position of mutations in DsbAss can hinder the translocation process of signal recognition particle system, thus affecting the virulence of bacteria.

Identification of activity related amino acid mutations of a GH9 termite cellulase

2010 ◽  
Vol 101 (16) ◽  
pp. 6438-6443 ◽  
Author(s):  
Jinfeng Ni ◽  
Motomi Takehara ◽  
Hirofumi Watanabe
Keyword(s):  
Amino Acid ◽  
Amino Acid Mutations ◽  
Related Amino Acid

Long-Time Scale Fluctuations of Human Prion Protein Determined by Restrained MD Simulations

Biochemistry ◽  
2011 ◽  
Vol 50 (47) ◽  
pp. 10192-10194 ◽  
Author(s):  
Massih Khorvash ◽  
Guillaume Lamour ◽  
Jörg Gsponer
Keyword(s):  
Prion Protein ◽  
Time Scale ◽  
Md Simulations ◽  
Long Time ◽  
Human Prion Protein ◽  
Restrained Md

scholarly journals The polyphenolic phytoalexin polydatin inhibits amyloid aggregation of recombinant human prion protein

RSC Advances ◽  
2021 ◽  
Vol 11 (42) ◽  
pp. 25901-25911
Author(s):  
Preeti Rana Sirohi ◽  
Anchala Kumari ◽  
Nikita Admane ◽  
Pallavi Somvanshi ◽  
Abhinav Grover
Keyword(s):  
Prion Protein ◽  
Amyloid Aggregation ◽  
Drug Lead ◽  
Human Prion Protein

Polydatin is found to be a pharmacologically-significant scaffold that can bind to the rPrPres repertoire and inhibit its conversion to the highly infectious and neurotoxic PrPSc-like form, thus acting like a promising anti-prion drug lead.

scholarly journals Genetic Variation and Evolution of the 2019 Novel Coronavirus

2021 ◽  
pp. 1-13
Author(s):  
Salvatore Dimonte ◽  
Muhammed Babakir-Mina ◽  
Taib Hama-Soor ◽  
Salar Ali
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Rapid Evolution ◽  
Single Amino Acid ◽  
Angiotensin Converting Enzyme 2 ◽  
New Type ◽  
Amino Acid Mutations ◽  
Host Infection ◽  
Human Coronaviruses ◽  
Novel Coronavirus

<b><i>Introduction:</i></b> SARS-CoV-2 is a new type of coronavirus causing a pandemic severe acute respiratory syndrome (SARS-2). Coronaviruses are very diverting genetically and mutate so often periodically. The natural selection of viral mutations may cause host infection selectivity and infectivity. <b><i>Methods:</i></b> This study was aimed to indicate the diversity between human and animal coronaviruses through finding the rate of mutation in each of the spike, nucleocapsid, envelope, and membrane proteins. <b><i>Results:</i></b> The mutation rate is abundant in all 4 structural proteins. The most number of statistically significant amino acid mutations were found in spike receptor-binding domain (RBD) which may be because it is responsible for a corresponding receptor binding in a broad range of hosts and host selectivity to infect. Among 17 previously known amino acids which are important for binding of spike to angiotensin-converting enzyme 2 (ACE2) receptor, all of them are conservative among human coronaviruses, but only 3 of them significantly are mutated in animal coronaviruses. A single amino acid aspartate-454, that causes dissociation of the RBD of the spike and ACE2, and F486 which gives the strength of binding with ACE2 remain intact in all coronaviruses. <b><i>Discussion/Conclusion:</i></b> Observations of this study provided evidence of the genetic diversity and rapid evolution of SARS-CoV-2 as well as other human and animal coronaviruses.

scholarly journals Sensitive protein misfolding cyclic amplification of sporadic Creutzfeldt–Jakob disease prions is strongly seed and substrate dependent

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maxime Bélondrade ◽  
Simon Nicot ◽  
Charly Mayran ◽  
Lilian Bruyere-Ostells ◽  
Florian Almela ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Misfolding ◽  
Protein Misfolding Cyclic Amplification ◽  
Bank Voles ◽  
Substrate Dependence ◽  
Brain Extracts ◽  
Jakob Disease ◽  
Human Prion Protein

AbstractUnlike variant Creutzfeldt–Jakob disease prions, sporadic Creutzfeldt–Jakob disease prions have been shown to be difficult to amplify in vitro by protein misfolding cyclic amplification (PMCA). We assessed PMCA of pathological prion protein (PrPTSE) from 14 human sCJD brain samples in 3 substrates: 2 from transgenic mice expressing human prion protein (PrP) with either methionine (M) or valine (V) at position 129, and 1 from bank voles. Brain extracts representing the 5 major clinicopathological sCJD subtypes (MM1/MV1, MM2, MV2, VV1, and VV2) all triggered seeded PrPTSE amplification during serial PMCA with strong seed- and substrate-dependence. Remarkably, bank vole PrP substrate allowed the propagation of all sCJD subtypes with preservation of the initial molecular PrPTSE type. In contrast, PMCA in human PrP substrates was accompanied by a PrPTSE molecular shift during heterologous (M/V129) PMCA reactions, with increased permissiveness of V129 PrP substrate to in vitro sCJD prion amplification compared to M129 PrP substrate. Combining PMCA amplification sensitivities with PrPTSE electrophoretic profiles obtained in the different substrates confirmed the classification of 4 distinct major sCJD prion strains (M1, M2, V1, and V2). Finally, the level of sensitivity required to detect VV2 sCJD prions in cerebrospinal fluid was achieved.

Sign in / Sign up

Export Citation Format

Share Document