Biochemical and biophysical interaction of rare earth elements with biomacromolecules: A comprehensive review.

The growing utilization of rare earth elements (REEs) in industrial and technological applications has captured global interest, leading to the development of high-performance technologies in medical diagnosis, agriculture, and other electronic industries. This accelerated utilization has also raised human exposure levels, resulting in both favourable and unfavourable impacts. However, the effects of REEs are dependent on their concentration and molecular species. Therefore, scientific interest has increased in investigating the molecular interactions of REEs with biomolecules. In this current review, particular attention was paid to the molecular mechanism of interactions of Lanthanum (La), Cerium (Ce), and Gadolinium (Gd) with biomolecules, and the biological consequences were broadly interpreted. The review involved gathering and evaluating a vast scientific collection which primarily focused on the impact associated with REEs, ranging from earlier reports to recent discoveries, including studies in human and animal models. Thus, understanding the molecular interactions of each element with biomolecules will be highly beneficial in elucidating the consequences of REEs accumulation in the living organisms.

Thermodynamics of benzoquinone-induced conformational changes in nucleic acids and human serum albumin.

Biological macromolecules such as proteins, nucleic acids, carbohydrates and lipids, play a crucial role in biochemical and molecular processes. Thus, the study of the structure-function relationship of biomolecules in presence of ligands is an important aspect of structural biology. The current communication describes the chemico-biological interaction between benzene metabolite para-benzoquinone (BQ) with B-form of nucleic acids (B-DNA) and human serum albumin (HSA). The binding ability of HSA towards bromocresol green (BCG) was significantly suppressed when exposed to increasing concentrations of BQ in the presence of various physiological buffers. Further, the native fluorescence of HSA was drastically reduced and the secondary structures of HSA were significantly compromised with increasing concentrations of BQ. In vitro and in silico studies also revealed that BQ binds to domains I and II of HSA and thus altering the conformation of HSA which may potentially affect plasma osmotic pressure, as well as the binding and transport of numerous endogenous and exogenous molecules. Similarly, BQ interacts directly to the GC region of B-DNA particularly in the minor groove which was also assessed by computational docking studies. Isothermal titration calorimetry data suggest higher binding affinity of BQ towards DNA than HSA. Various spectroscopic observations also suggest that BQ binds to DNA preferably in the minor grooves. Thus, the results revealed that BQ may play a key role in inducing mutagenicity, either by formation of adducts on GC regions or by accelerating oxidative damage to biomacromolecules through chemico-biological interactions.

Compromised conformation and kinetics of catalase in the presence of propylthiouracil: A biophysical study and alleviation by curcumin.

In the present study, the inhibitory effect of propylthiouracil (PTU) on bovine liver catalase (BLC) activity was studied in the presence of curcumin (CUR). The results suggest that the PTU-induced decrease in BLC activity was caused by a change in conformation of BLC with reduced α-helical content and decrease in zeta potential. Nevertheless, temperature-dependent activation of CUR protects the activity of BLC by restoring the secondary conformation and zeta potential of BLC. CUR inhibited the time-induced reduction in BLC activity and the protection was increased with increasing concentrations of CUR and found to be significant even from 1:0.1 molar ratios. The enzyme kinetics confirmed the high catalytic efficiency of BLC in presence of CUR than PTU. The protective role of CUR was due to the formation of a more stabilized complex as demonstrated by molecular docking, and fourier-transform infrared study. Isothermal titration calorimetric study supports for a favourable reaction between BLC and PTU or CUR due to the negative ΔH, and positive TΔS. Although the number of binding sites for PTU and CUR was found to be 10 and 7, respectively, the binding affinity between CUR and BLC is approximately 3.72 fold stronger than BLC-PTU complex. The increased melting temperature of BLC was noticed in presence of CUR suggesting the protective potential of CUR towards biomolecules. Indeed, this is the first biophysical study to describe the molecular mechanism of PTU-induced reduction in BLC activity and alleviation by CUR with detail kinetics. Thus, CUR can be further extended to other antioxidant enzymes or compromised biomolecules for therapeutic interventions.

Interaction of artemisinin protects the activity of antioxidant enzyme catalase: A biophysical study.

The major antioxidant enzyme catalase is downregulated and the enzyme activity is compromised in various disease conditions such as malarial and cancer. Hence, the restoration and protection of catalase is a promising therapeutic strategy in disease management. In the present study, for the first time we have demonstrated the protective role of well-known anti-malarial drug Artemisinin (ART) on the time and temperature-induced degradation of bovine liver catalase (BLC) activity. The findings at different time intervals and at higher temperature showed the protective role of ART on BLC activity. Molecular docking studies suggested specific binding of ART on BLC through heme group interface which was further supported by cyclic voltammetry and dynamic light scattering study. The stabilization of BLC in presence of ART was mediated through forming a BLC-ART complex with reduced and shifted electrochemical peak and increased hydrodynamic diameter. ART substantially prevents the temperature-induced reduction in α-helical content with simultaneous increment in other secondary structures like antiparallel, parallel, ß-turn and random coils. Nevertheless, the protective role of ART was accepted from the enhanced thermal stability and increased Tm value of BLC in presence of ART at higher temperatures. Our results uncover the mechanism of interaction between ART with BLC and suggest the protective role of ART towards spatiotemporal alteration of BLC by preventing the structural and molecular change in BLC. Thus, the findings advocate ART as a potential therapeutic drug for diseases associated with reduced catalase activity.

The benzene metabolite p-benzoquinone inhibits the catalytic activity of bovine liver catalase: A biophysical study.

The current communication reports the inhibitory effect of para-benzoquinone (p-BQ) on the structure and function of bovine liver catalase (BLC), a vital antioxidant enzyme. Both BLC and p-BQ were dissolved in respective buffers and the biophysical interaction was studied at physiological concentrations. For the first time our data reveals an enthalpy-driven interaction between BLC and p-BQ which is due to hydrogen bonding and van der Waals interactions. The binding affinity of p-BQ with BLC is nearly 2.5 folds stronger in MOPS buffer than Phosphate buffer. Importantly, the binding affinity between BLC and p-BQ was weak in HEPES buffer as compared to other buffers being the strongest in Tris buffer. Molecular docking studies reveal that binding affinity of p-BQ with BLC differ depending upon the nature of buffers rather than on the participating amino acid residues of BLC. This is further supported by the differential changes in secondary structures of BLC. The p-BQ-induced conformational change in BLC was evident from the reduced BLC activity in presence of different buffers in the following order, Phosphate>MOPS>Tris>HEPES. The absorbance peak of BLC was gradually increased and fluorescence spectra of BLC were drastically decreased when BLC to p-BQ molar ratio was incrementally enhanced from 0 to 10,000 times in presence of all buffers. Nevertheless, the declined activity of BLC was positively correlated with the reduced fluorescence and negatively correlated with the enhanced absorbance. Electrochemical study with cyclic voltammeter also suggests a direct binding of p-BQ with BLC in presence of different buffers. Thus, p-BQ-mediated altered secondary structure in BLC results into compromised activity of BLC.

Differential interaction of cerium chloride with bovine liver catalase: A computational and biophysical study.

In this study, Cerium chloride-induced conformational changes of Bovine Liver Catalase (BLC) has been investigated by molecular docking and further supported by various biophysical techniques. The temporal change of catalytic activity of BLC has also been studied in presence of Ce(III) with different buffer solution in vitro at 25 °C. The differential binding of Ce(III) to BLC observed by simulation study was well supported by the differential regulation of BLC activity in different buffers. After 1 h of incubation with CeCl3, the reduction in activity of BLC was maximum in MOPS, HEPES and Tris buffer, whereas no change in activity was noticed in phosphate buffer. Isothermal Titration Calorimetric (ITC) study also supports the differential binding of Ce(III) to BLC in different buffers. Ce(III)-induced conformational transition in BLC was followed as a function of concentration. Nevertheless, with 24 h incubation of CeCl3 the activity of BLC was highest with higher molar concentration of CeCl3 suggesting the conformational stability of BLC in presence of Ce(III). The compromised activity of BLC in response to Ce(III) is due to the induced conformational change and the degree of change in secondary conformation of BLC was maximum in MOPS, HEPES and Tris and least in phosphate buffer. Therefore, the reduced activity of BLC is controlled by the direct interaction of Ce(III) in the active site of BLC in Tris buffer or indirect interaction of Ce(III) in the non-active site of BLC in MOPS and HEPES buffer.

Lanthanum chloride-induced conformational changes of bovine liver catalase: A computational and biophysical study.

We have investigated the effects of lanthanum chloride (LaCl3) on catalytic activity and conformation of bovine liver catalase (BLC) in different buffer solutions in vitro at 25 °C. Higher concentration of the salt caused decrease in catalase activity in the following order, HEPES > MOPS > Tris > Phosphate buffer. Results obtained from circular dichroism, fluorescence and absorption spectroscopy and from computational docking studies indicate that reduction in activity of BLC by LaCl3 is due to induction of conformational changes. Lanthanum-induced reduced BLC activity in MOPS, HEPES and Tris buffer is characterized by a significant loss in native fluorescence and increase in absorbance spectra of BLC. Nevertheless, the change in secondary conformation of BLC was maximum in HEPES and MOPS followed by Tris and least in Phosphate buffer. Therefore, the significant loss of BLC activity in phosphate buffer at higher molar concentration of lanthanum is attributed to the change in buffering capacity of the buffer. The conformational transition of BLC by LaCl3 was followed as a function of concentration. Therefore, the reduced BLC activity is directly controlled by lanthanum-induced conformational change of BLC in HEPES, MOPS and Tris buffer and indirectly controlled by the change in buffering capacity of the phosphate buffer.