Exploring the Specific Role of Iron Center in the Catalytic Activity of Human Serum Transferrin: CTAB-Induced Conformational Changes and Sequestration by Mixed Micelles

Conformational changes play a seminal role in modulating the activity of proteins. This concept becomes all the more relevant in the context of metalloproteins, owing to the formation of specific conformation(s) induced by internal perturbations (like a change in pH, ligand binding, or receptor binding), which may carry out the binding and release of the metal ion/ions from the metal binding center of the protein. Herein, we investigated the conformational changes of an iron-binding protein, monoferric human serum transferrin (Fe-hTF), using several spectroscopic approaches. We could reversibly tune the cetyltrimethylammonium bromide (CTAB)-induced conformation of the protein, exploiting the concept of mixed micelles formed by three sequestrating agents: (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) hydrate (CHAPS) and two bile salts, namely, sodium cholate (NaC) and sodium deoxycholate (NaDC). The formation of mixed micelles between CTAB and these reagents (CHAPS/NaC/NaDC) results in the sequestration of CTAB molecules from the protein environment and aids the protein in reattaining its native-like structure. However, the guanidinium hydrochloride-induced denatured Fe-hTF did not acquire its native-like structure using these sequestrating agents, which substantiates the exclusive role of mixed micelles in the present study. Apart from this, we found that the conformation of transferrin (adopted in the presence of CTAB) displays pronounced esterase-like activity toward the para-nitrophenyl acetate (PNPA) substrate as compared to native transferrin. We also outlined the impact of the iron center and amino acids surrounding the iron center on the effective catalytic activity in the CTAB medium. We estimated ∼3 times higher specific catalytic efficiency for the iron-depleted Apo-hTF compared to the fully iron-saturated Fe2-hTF in the presence of CTAB

White Light Generation through l‑Ascorbic Acid-Templated Thermoresponsive Copper Nanoclusters

Owing to their lower toxicity and tuneable optical properties, luminescent copper nanoclusters (CuNCs) have emerged as a new generation of materials with multidiverse applications in cellular imaging, sensing, and optoelectronics. However, the preparation of highly stable CuNCs using a small ligand as a template still serves as a bottleneck in the development of nanoclusters. Herein, we report ascorbic acid (AA)-templated blue-emitting CuNCs that display excellent thermoresponsive properties within a temperature range of 25–65 °C. Interestingly, our as-prepared CuNCs can generate white light emission (WLE) when mixed with bovine serum albumin (BSA)-templated red-emitting silver nanoclusters (AgNCs) under optimized conditions. The WLE so generated was characterized by the Commission Internationale d’Eclairage (CIE) coordinates of (0.33, 0.30), a color rendering index (CRI) of 80, and a correlated color temperature (CCT) of 5624 K, parameters that are very close to those of pure white light. The cell viability data and confocal laser scanning microscopy images of HeLa cells obtained using these CuNCs substantiate their nontoxic and biocompatible nature

Polymer nano-biocomposite based on poly (ethylene-co-methyl acrylate) (EMA)/cellulose nanocrystals (CNC); preparation and properties

In addition to being bio-degradable, cellulose nanocrystals (CNC) provide high mechanical strength to polymer composites. They exhibit outstanding properties like high strength-to-weight ratio, abundant surface functional groups and sustainability. In this study, we prepared nanocomposites of poly (ethylene-co-methyl acrylate) (EMA) and CNC using the melt-mixing technique. The mechanical properties of EMA were improved after adding CNC to it. The ultimate tensile stress and maximum elongation increased from 6 MPa and 860% (for pristine EMA) to 9.5 MPa and 1090% (for 2 wt.% EMA/CNC composite). Thermal properties of the EMA/CNC composites were analyzed by using DSC and TGA analysis. The dispersion of CNC in the composite was analyzed by SEM and XRD analyses. The EMA/CNC composites showed interesting birefringence properties on analysis via polarized optical microscopy (POM). The POM analysis indicated that the CNC in composites aligns themselves in the direction of applied stress, enhancing the mechanical strength of nanocomposites. Biodegradation of the bio-composite was also studied via soil-burial test.</p

Structure-Based Design of Inhibitors with Improved Selectivity for Steroidogenic Cytochrome P450 17A1 over Cytochrome P450 21A2

Inhibition of androgen biosynthesis is clinically effective for treating androgen-responsive prostate cancer. Abiraterone is a clinical first-in-class inhibitor of cytochrome P450 17A1 (CYP17A1) required for androgen biosynthesis. However, abiraterone also causes hypertension, hypokalemia, and edema, likely due in part to off-target inhibition of another steroidogenic cytochrome P450, CYP21A2. Abiraterone analogs were designed based on structural evidence that B-ring substituents may favorably interact with polar residues in binding CYP17A1 and sterically clash with residues in the CYP21A2 active site. The best analogs increased selectivity of CYP17A1 inhibition up to 84-fold compared with 6.6-fold for abiraterone. Cocrystallization with CYP17A1 validated the intended new contacts with CYP17A1 active site residues. Docking these analogs into CYP21A2 identified steric clashes that likely underlie decreased binding and CYP21A2 inhibition. Overall, these analogs may offer a clinical advantage in the form of reduced side effects

Structure-Based Design of Inhibitors with Improved Selectivity for Steroidogenic Cytochrome P450 17A1 over Cytochrome P450 21A2

Inhibition of androgen biosynthesis is clinically effective for treating androgen-responsive prostate cancer. Abiraterone is a clinical first-in-class inhibitor of cytochrome P450 17A1 (CYP17A1) required for androgen biosynthesis. However, abiraterone also causes hypertension, hypokalemia, and edema, likely due in part to off-target inhibition of another steroidogenic cytochrome P450, CYP21A2. Abiraterone analogs were designed based on structural evidence that B-ring substituents may favorably interact with polar residues in binding CYP17A1 and sterically clash with residues in the CYP21A2 active site. The best analogs increased selectivity of CYP17A1 inhibition up to 84-fold compared with 6.6-fold for abiraterone. Cocrystallization with CYP17A1 validated the intended new contacts with CYP17A1 active site residues. Docking these analogs into CYP21A2 identified steric clashes that likely underlie decreased binding and CYP21A2 inhibition. Overall, these analogs may offer a clinical advantage in the form of reduced side effects

sj-docx-1-cpc-10.1177_10556656221080359 - Supplemental material for Cone-Beam Computed Tomographic Assessment of Maxillary Sinus Characteristics in Patients With Cleft Lip and Palate: A Systematic Review and Meta-Analysis

Supplemental material, sj-docx-1-cpc-10.1177_10556656221080359 for Cone-Beam Computed Tomographic Assessment of Maxillary Sinus Characteristics in Patients With Cleft Lip and Palate: A Systematic Review and Meta-Analysis by Sukeshana Srivastav, Nitesh Tewari, Ritu Duggal, Shubhi Goel, Morankar Rahul, Vijay Prakash Mathur, Rahul Yadav and Ashish Dutt Upadhyaya in The Cleft Palate-Craniofacial Journal</p

Legislative Documents

Also, variously referred to as: House bills; House documents; House legislative documents; legislative documents; General Court documents

Structure-Based Design of Inhibitors with Improved Selectivity for Steroidogenic Cytochrome P450 17A1 over Cytochrome P450 21A2

Inhibition of androgen biosynthesis is clinically effective for treating androgen-responsive prostate cancer. Abiraterone is a clinical first-in-class inhibitor of cytochrome P450 17A1 (CYP17A1) required for androgen biosynthesis. However, abiraterone also causes hypertension, hypokalemia, and edema, likely due in part to off-target inhibition of another steroidogenic cytochrome P450, CYP21A2. Abiraterone analogs were designed based on structural evidence that B-ring substituents may favorably interact with polar residues in binding CYP17A1 and sterically clash with residues in the CYP21A2 active site. The best analogs increased selectivity of CYP17A1 inhibition up to 84-fold compared with 6.6-fold for abiraterone. Cocrystallization with CYP17A1 validated the intended new contacts with CYP17A1 active site residues. Docking these analogs into CYP21A2 identified steric clashes that likely underlie decreased binding and CYP21A2 inhibition. Overall, these analogs may offer a clinical advantage in the form of reduced side effects

sj-docx-3-cpc-10.1177_10556656221080359 - Supplemental material for Cone-Beam Computed Tomographic Assessment of Maxillary Sinus Characteristics in Patients With Cleft Lip and Palate: A Systematic Review and Meta-Analysis

Supplemental material, sj-docx-3-cpc-10.1177_10556656221080359 for Cone-Beam Computed Tomographic Assessment of Maxillary Sinus Characteristics in Patients With Cleft Lip and Palate: A Systematic Review and Meta-Analysis by Sukeshana Srivastav, Nitesh Tewari, Ritu Duggal, Shubhi Goel, Morankar Rahul, Vijay Prakash Mathur, Rahul Yadav and Ashish Dutt Upadhyaya in The Cleft Palate-Craniofacial Journal</p

Structure-Based Design of Inhibitors with Improved Selectivity for Steroidogenic Cytochrome P450 17A1 over Cytochrome P450 21A2

Inhibition of androgen biosynthesis is clinically effective for treating androgen-responsive prostate cancer. Abiraterone is a clinical first-in-class inhibitor of cytochrome P450 17A1 (CYP17A1) required for androgen biosynthesis. However, abiraterone also causes hypertension, hypokalemia, and edema, likely due in part to off-target inhibition of another steroidogenic cytochrome P450, CYP21A2. Abiraterone analogs were designed based on structural evidence that B-ring substituents may favorably interact with polar residues in binding CYP17A1 and sterically clash with residues in the CYP21A2 active site. The best analogs increased selectivity of CYP17A1 inhibition up to 84-fold compared with 6.6-fold for abiraterone. Cocrystallization with CYP17A1 validated the intended new contacts with CYP17A1 active site residues. Docking these analogs into CYP21A2 identified steric clashes that likely underlie decreased binding and CYP21A2 inhibition. Overall, these analogs may offer a clinical advantage in the form of reduced side effects