Inter-helical angles and distances between helices α₂ and α₃ in high-resolution structures of PrP^C proteins ^a.

a<p>Calculated with Chimera system <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011715#pone.0011715-Pettersen1" target="_blank">[59]</a>.</p

Structural comparison of HuPrP mutants.

<p>(A) Structural details of β₂α₂α₃α₄ region (161–228) of 20 lowest energy structures for HuPrP(90–231, M129, Q212P) mutant. (B) Structural details of β₂α₂α₃ region (161–228) of 20 lowest energy structures for HuPrP(90–231, M129, R220K) (pdb id 1E1U) mutant <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011715#pone.0011715-Calzolai1" target="_blank">[31]</a>. (C) Structural details of β₂α₂α₃ region (161–228) of 20 lowest energy structures for HuPrP(90–231, M129, E200K) (pdb id 1FO7) mutant <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011715#pone.0011715-Zhang1" target="_blank">[28]</a>. In all three panels the point mutation is indicated in magenta (left). Top view of the hydrophobic core composed of aromatic amino acid residues (center). Hydrophobicity surface is presented on the right, where red color indicates hydrophobic and blue color represents hydrophilic surface.</p

Distances between Tyr225 and residues within β₂–α₂ loop region and α₃ helix.

a<p>All presented data are average distances and standard deviations in Å calculated for ensemble of 20 structures deposited in pdb.</p>b<p>Distances between carbons Tyr169 C_α and Tyr225 C_α.</p>c<p>Distances between carbons Met166 C_α and Tyr225 C_α.</p>d<p>Distances between carbons Ile215 C_δ1 and Tyr225 C_z.</p

¹⁵N relaxation rates for HuPrP(90–231, M129, Q212P) protein at 298K.

<p>¹⁵N longitudinal (<i>R</i>₁), transverse (<i>R</i>₂) relaxation rates and heteronuclear {¹H}-¹⁵N NOE data acquired at 11.7 T and 16.4 T shown in blue and red, respectively.</p

Impact of Calcium Binding and Thionylation of S100A1 Protein on Its Nuclear Magnetic Resonance-Derived Structure and Backbone Dynamics

S100 proteins play a crucial role in multiple important biological processes in vertebrate organisms acting predominantly as calcium signal transmitters. S100A1 is a typical representative of this family of proteins. After four Ca²⁺ ions bind, it undergoes a dramatic conformational change, resulting in exposure, in each of its two identical subunits, a large hydrophobic cleft that binds to target proteins. It has been shown that abnormal expression of S100A1 is strongly correlated with a number of severe human diseases: cardiomyopathy and neurodegenerative disorders. A few years ago, we found that thionylation of Cys 85, the unique cysteine in two identical S100A1 subunits, leads to a drastic increase of the affinity of the protein for calcium. We postulated that the protein activated by thionylation becomes a more efficient calcium signal transmitter. Therefore, we decided to undertake, using nuclear magnetic resonance methods, a comparative study of the structure and dynamics of native and thionylated human S100A1 in its apo and holo states. In this paper, we present the results obtained for both forms of this protein in its holo state and compare them with the previously published structure of native apo-S100. The main conclusion that we draw from these results is that the increased calcium binding affinity of S100A1 upon thionylation arises, most probably, from rearrangement of the hydrophobic core in its apo form

Distance restrains per residue.

<p>(A) Type of NOE used in structure calculations of HuPrP(90–231, M129, Q212P) protein. (B) Enlarged region between Tyr218 and Tyr225. Glu221 and Ser222 do not exhibit any long-range NOE contacts. (C) Schematic presentation of long-range NOE contacts (|i-j|>5) between residues in helices a₃ and a₄. For clarity, only inter-helical NOE contacts are shown.</p

Synthesis, structural characterization and antitumor activities of manganese and cobalt isothiocyanate complexes with 2,2’-bipyridine

[Mn(SCN)2(2,2′-bipy)2] (1) and [Co(SCN)2(2,2′-bipy)2] (2) were synthesized at ambient temperature by adding aqueous solutions of manganese(II) or cobalt(II) chloride hydrate to aqueous acetonitrile solutions of 2,2′-bipyridine (2,2′-bipy) and potassium thiocyanate. Elemental analyses, FT-IR and UV–vis spectra were used to characterize 1 and 2. Single crystal X-ray diffraction was used to analyze the crystal structures of 1 and 2, revealing that the two are structurally similar. The molecular structures of 1 and 2 consist of Mn or Co ion chelated by two molecules of 2,2′-bipy through four nitrogen atoms and two NCS anions, giving distorted octahedral geometries. The isothiocyanate group is not bridging, instead, two ligands coordinate in a cis arrangement to the manganese or cobalt center by their nitrogen atoms while the sulfur atoms are free. Through hydrogen bonding and π–π stacking interactions, the discrete units of 1 and 2 extend to 3D supramolecular networks with flower and fishbone-like structures. The luminescence behavior of 2,2′-bipy, 1 and 2 were investigated. On HepG2 (liver) and MCF-7 (breast) cancer cells, the anticancer effects of 1 and 2 were evaluated. The activity of 1 and 2 on MCF-7 is more significant than that of HepG2. The IC50 of 1 was lower in HepG2 and MCF-7 cells than for 2. </p

Inhibition of the predicted allosteric site of the SARS-CoV-2 main protease through flavonoids

Since its emergence in 2019, coronavirus infection (COVID-19) has become a global pandemic and killed several million people worldwide. Even though several types of vaccines are available against the COVID-19 virus, SARS-CoV-2, new strains are emerging that pose a constant danger to vaccine effectiveness. In this computational study, we identified and predicted potent allosteric inhibitors of the SARS-CoV-2 main protease (Mpro). Via molecular docking and simulations, more than 100 distinct flavonoids were docked with the allosteric site of Mpro. Docking experiments revealed four top hit compounds (Hesperidin, Schaftoside, Brickellin, and Marein) that bound strongly to the Mpro predicted allosteric site. Simulation analyses further revealed that these continually interacted with the enzyme’s allosteric region throughout the simulation time. ADMET and Lipinski drug likenesses were calculated to indicate the therapeutic value of the top four hits: They were non-toxic and exhibited high human intestinal absorption concentrations. These novel allosteric site inhibitors provide a higher chance of drugging SARS-CoV2 Mpro due to the rapid mutation rate of the viral enzyme’s active sites. Our findings provide a new avenue for developing novel allosteric inhibitors of SARS-CoV-2 Mpro. Communicated by Ramaswamy H. Sarma</p

Data_Sheet_1_Genetic basis and principal component analysis in cotton (Gossypium hirsutum L.) grown under water deficit condition.docx

Cotton is considered as the main crop in the agricultural sector of Pakistan. Water deficiency in this region in recent years has reduced the chances of high yields of cotton. Selection and creation of high-yielding varieties of cotton, even in water deficit conditions, is one of urgent tasks of today. For this purpose, 40 diverse genotypes of upland cotton were screened in normal and water deficit conditions in triplicate arrangement under split plot in a randomized complete block design. All the genotypes showed significant difference under both water regimes. Ten upland cotton accessions were screened out as water deficit tolerant (VH-144, IUB-212, MNH-886, VH-295, IR-3701, AA-802, NIAB-111, NS-121, FH-113, and FH-142) and five as water deficit sensitive (IR-3, CIM-443, FH-1000, MNH-147, and S-12) based on seed cotton yield and stress susceptibility index. These tolerant and sensitive genotypes were crossed in line × tester mating design. For further evaluation of genetic material, the seed of 50 F1 crosses and their 15 parents were field planted under normal and water deficit conditions during next cotton growing season. Traits related to yield under the study showed significant variations among the accessions and their half sibs. The results of the principal component analysis (PCA) exhibited that total variation exhibited by factors 1 and factor 2 were 55.55 and 41.95%, respectively. PCA transformed the variables into three factors, and only two factors (F1 and F2) had eigenvalue > 1. The degree of dominance revealed that all parameters were highly influenced by non-additive gene action under both water regimes. Furthermore, the line VH-295 and tester CIM-443 had better yield performance under water deficit stress. The cross-combinations, viz., VH-144 × S-12, NIAB-111 × IR-3, and VH-295 × MNH-147, were the best for yield contributing traits. These combinations may be helpful for germplasm enhancement on large scale under water scarcity. All the studied traits have non-additive types of gene action suggesting the usage of these genotypes in cotton hybrid development program against water deficit tolerance.</p

Table_1_Exploring the antibacterial potential of plant extracts and essential oils against Bacillus thermophilus in beet sugar for enhanced sucrose retention: a comparative assessment and implications.pdf

Sugar beet is one of the greatest sources for producing sugar worldwide. However, a group of bacteria grows on beets during the storage process, leading to a reduction in sucrose yield. Our study focused on identifying common bacterial species that grow on beets during manufacturing and contribute to sucrose loss. The ultimate goal was to find a potential antibacterial agent from various plant extracts and oils to inhibit the growth of these harmful bacteria and reduce sucrose losses. The screening of bacterial species that grow on beet revealed that a large group of mesophilic bacteria, such as Bacillus subtilis, Leuconostoc mesenteroides, Pseudomonas fluorescens, Escherichia coli, Acinetobacter baumannii, Staphylococcus xylosus, Enterobacter amnigenus, and Aeromonas species, in addition to a dominant thermophilic species called Bacillus thermophilus, were found to be present during the manufacturing of beets. The application of 20 plant extracts and 13 different oils indicated that the extracts of Geranium gruinum, Datura stramonium, and Mentha spicata were the best antibacterials to reduce the growth of B. thermophilus with inhibition zones equal to 40, 39, and 35 mm, respectively. In contrast, the best active oils for inhibiting the growth of B. thermophilus were Mentha spicata and Ocimum bacilicum, with an inhibitory effect of 50 and 45 mm, respectively. RAPD-PCR with different primers indicated that treating sugar juice with the most effective oils against bacteria resulted in new recombinant microorganisms, confirming their roles as strong antibacterial products. The characterization of Mentha spicata and Ocimum bacilicum oils using GC/MS analysis identified cis-iso pulegone and hexadecanoic acid as the two main bioactive compounds with potential antibacterial activity. An analysis of five genes using DD-PCR that have been affected due to antibacterial activity from the highly effective oil from Mentha spicata concluded that all belonged to the family of protein defense. Our findings indicate that the application of these pure antibacterial plant extracts and oils would minimize the reduction of sucrose during sugar production.</p