Biomolecular Concepts最新文献

Antibodies have transformed biomedical research and are now being used for different experimental applications. Generally, the interaction of enzymes with their specific antibodies can lead to a reduction in their enzymatic activity. The effect of the antibody is dependent on its narrow i.e. the regions of the enzyme to which it is directed. The mechanism of this inhibition is rarely a direct combination of the antibodies with the catalytic site, but is rather due to steric hindrance, barring the substrate access to the active site. In several systems, however, the interaction with the antibody induces conformational changes on the enzyme that can either inhibit or enhance its catalytic activity. The extent of enzyme inhibition or enhancement is, therefore, a reflection of the nature and distribution of the various antigenic determinants on the enzyme molecule. Currently, the mode of action of many enzymes has been elucidated at the molecular level. We here review the molecular mechanisms and recent trends by which antibodies inhibit the catalytic activity of enzymes and provide examples of how specific antibodies can be useful for the neutralization of biologically active molecules.

Out of seven Fusarium spp. isolated from infected faba bean roots, two Fusarium oxysporum were selected and showed faba bean-wilt disease severity with percentages of 68% and 47% under greenhouse conditions. The F. oxysporum showed the highest wilt disease was selected to complete the current study. Three rhizobacterial strains were isolated and identified as Bacillus velezensis Vb1, B. paramycoides Vb3, and B. paramycoides Vb6. These strains showed the highest in-vitro antagonistic activity by the dual-culture method against selected F. oxysporum with inhibition percentages of 59±0.2, 46±0.3, and 52±0.3% for Vb1, Vb3, and Vb6, respectively. These rhizobacterial strains exhibit varied activity for nitrogen-fixing and phosphate-solubilizing. Moreover, these strains showed positive results for ammonia, HCN, and siderophores production. The phytohormones production (indole-3-acetic acid, ABA, benzyl, kinten, ziaten, and GA₃) and secretion of various lytic enzymes were recorded by these strains with varying degrees. Under greenhouse conditions, the rhizobacterial strains Vb1, Vb3, Vb6, and their consortium can protect faba bean from wilt caused by F. oxysporum with percentages of 70, 60, 65, and 82%, respectively. Under field conditions, the inoculation with the rhizobacterial consortium (Vb1+Vb3+Vb6) significantly increases the growth performance of the F. oxysporum-infected faba bean plant and recorded the highest wilt protection (83.3%).

Nowadays, mutations in the epidermal growth factor receptor (EGFR) kinase domain are studied in targeted therapy of non-small cell lung cancer (NSCLC) with EGFR tyrosine kinase inhibitors including gefitinib and erlotinib. The present study reports a rare case of a patient harboring three simultaneous EGFR mutations (L718A, Q849H, and L858R). The development of erlotinib resistance was detected in the subsequent treatment. Using a computational approach, the current study investigated the conformational changes of wild-type and mutant EGFR's kinase domains in the interaction with erlotinib. Their binding modes with erlotinib were elucidated during molecular dynamics simulation, where higher fluctuations were detected in the mutated forms of the EGFR tyrosine kinase domain. Prediction of stability and functional effect of mutations revealed that amino acidic substitutions have decreased the protein stability as well as the binding affinity to erlotinib. These results may be useful for a recommendation of EGFR mutational analysis for patients with NSCLC carcinoma.

The main objective of the current study was to improve the essential oil contents of Thymus vulgaris L. using bio-inoculation with bacterial endophytes. Therefore, out of fourteen endophytic bacterial isolates obtained from roots of T. vulgaris, five isolates were selected based on the highest nitrogen-fixation and phosphate solubilization activity and identified as: Bacillus haynesii T9r, Citrobacter farmeri T10r, Bacillus licheniformis T11r, Bacillus velezensis T12r, and Bacillus velezensis T13r. These five strains have been recorded as ammonia, hydrogen cyanide (HCN), siderophores, and indole-3-acetic acid (IAA) producers. These strains have the efficacy to fix-nitrogen by reduction of acetylene with values of 82.133±1.4-346.6±1.4 n-mole-C₂H₄/ml/24 h. The IAA, gibberellic acid, abscisic acid, benzyl, kinten, and ziaten production were confirmed using HPLC. Two strains of T11r and T13r showed the highest plant growth-promoting properties and were selected for bio-inoculation of T. vulgaris individually or in a consortium with different mineral fertilization doses (0, 50, 75, and 100%) under field conditions. The highest growth performance was attained with the endophytic consortium (T11r+T13r) in the presence of 100% mineral fertilization. The GC-MS analysis of thyme oil contents showed the presence of 23 various compounds with varying percentages and the thymol fraction represented the highest percentages (39.1%) in the presence of the bacterial consortium.

Studies published earlier this year demonstrated the association of the solute carrier SLC6A20 gene with the risk and severity of COVID-19. The SLC6A20 protein product (Sodium-dependent Imino Transporter 1 (SIT1)) is involved in the transport of amino acids, including glycine. Here we summarized the results of recent studies demonstrating the interaction of SIT1 with the ACE2 receptor for SARS-CoV-2 as well as an observed association of SLC6A20 with the risk and traits of Type 2 diabetes (T2D). Recently, it was also proposed that SLC6A20 represents the novel regulator of glycine levels and that glycine has beneficial effects against the proinflammatory cytokine secretion induced by SARS-CoV-2 infection. Ivermectin, as a partial agonist of glycine-gated chloride channels, was also recently suggested to interfere with the COVID-19 cytokine storm by inducing the activation of glycine receptors. Furthermore, plasma glycine levels are found to be decreased in diabetic patients. Thus, further clinical trials are warranted to confirm the potential favorable effects of targeting the SIT1 transporter and glycine levels in the treatment of COVID-19, particularly for the severe case of disease associated with hyperglycemia, inflammation, and T2D. These findings suggest that SIT1 may potentially represent one of the missing pieces in the complex puzzle observed between these two pandemic diseases and the potential novel target for their efficient treatment.

The BCR-ABL oncogene is a tyrosine kinase gene that is over-expressed in CML. It inhibits the TGF-β1 signaling pathway. Due to resistance of cells to the tyrosine kinase inhibitor, STI-571, the combined effect of STI-571 and TGF-β1 on K562 cells was studied in the present research. Results revealed that the TGF-β1 cell signaling pathway, which is activated in K562 cells treated with TGF-β1, activates collective cell signaling pathways involved in survival and apoptosis. It is noteworthy that treating K562 cells with STI-571 triggered apoptotic pathways, accompanied by a reduction in proteins such as Bcl-xL, Bcl-2, p-AKT, p-Stat5, p-FOXO3, and Mcl-1 and an increase in the pro-apoptotic proteins PARP cleavage, and p27, leading to an increase in sub-G1 phase-arrested and Annexin-positive cells. Interestingly, the proliferation behavior of TGF-β1-induced cells was changed with the combination therapy, and STI-571-induced apoptosis was also prompted by this combination. Thus, combination treatment appears to promote sub-G1 cell cycle arrest compared to individually treated cells. Furthermore, it strongly triggered apoptotic signaling. In conclusion, TGF-β1 did not negatively impact the effect of STI-571, based on positive annexin cells, and AKT protein phosphorylation remains effective in apoptosis.