Theoretical investigation on hydrolysis mechanism of cis-platin analogous Pt(II)/Pd(II) complex by DFT calculation and molecular docking approach for their interaction with DNA & HSA.

The properties to be an active drug candidate of the complex Pt(TEEDA)Cl2, C1; Pd(TEEDA)Cl2, C2 and their hydrolysed product [Pt(TEEDA)(OH2)2]2+, C1' and [Pd(TEEDA)(OH2)2]2+, C2' were predicted by Lipinski's rule of 5 and PASS (prediction of activity spectra for substances) web tool. Their structural profile, HOMO-LUMO energy and electronic potential surface ware analysed by DFT calculation. Their TD-DFT spectra were compared with experimental UV-Vis spectra. The hydrolysis mechanisms of C1 & C2 to the diaqua form C1' and C2' were extensively investigated by DFT method in different levels of theory and using CPCM/water model and compared with recognised Pt based anticancer drugs. All the stationary states, including the transition state for the reactions were identified by the DFT calculation. The IRC calculation confirmed that the transition states are well connected and corelate with reactants and products. Interaction of the complexes with DNA & HSA was also investigated by molecular docking study.

Computational approach for identification, characterization, three-dimensional structure modelling and machine learning-based thermostability prediction of xylanases from the genome of Aspergillus fumigatus.

Identification of thermostable and alkaline xylanases from different fungal and bacterial species have gained an interest for the researchers because of its biotechnological relevance in many industries, such as pulp, paper, and bioethanol. In this study, we have identified and characterized xylanases from the genome of the thermophilic fungus of Aspergillus fumigatus by in silico analysis. Genome data mining revealed that the A fumigatus genome has six xylanase genes that belong to GH10, GH11, GH43 glycoside hydrolase families. In general, most of the bacterial and fungal GH11 xylanases are alkaline, and GH10 xylanases are acidic; however, we found that one identified xylanase from A fumigatus that belongs to the GH10 family is alkaline while the rest are acidic. Moreover, physicochemical properties also stated that most of the xylanases identified have lower molecular weight except one that belongs to the GH43 family. Structure prediction by homology modelling gave optimized structures of the xylanases. It suggests that GH10 family structure models adapt (ß∕α) 8 barrel type, GH11 homology models adapt ß-jelly type, and the GH43 family has a fivefold ß-propeller type structure. Molecular docking of identified xylanases with xylan revealed that GH11 xylanases have strong interaction (-9.6 kcal/mol) with xylan than the GH10 (-8.5 and -9.3 kcal/mol) and GH43 (-8.8 kcal/mol). We used the machine learning approach based TAXyl server to predict the thermostability of the xylanases. It revealed that two GH10 xylanases and one GH11 xylanase are thermo-active up to 75ᵒC. We have explored the physiochemical properties responsible for maintaining thermostability for bacterial and fungal GH10 and GH11 xylanases by comparing crystal structures. All the analyzed parameters specified that GH10 xylanases from both the fungi and bacteria are more thermostable due to higher hydrogen bonds, salt bridges, and helical content.

Loss of Mitochondrial Localization of Human FANCG Causes Defective FANCJ Helicase.

Fanconi anemia (FA) is a unique DNA damage repair pathway. To date, 22 genes have been identified that are associated with the FA pathway. A defect in any of those genes causes genomic instability, and the patients bearing the mutation become susceptible to cancer. In our earlier work, we identified that Fanconi anemia protein G (FANCG) protects the mitochondria from oxidative stress. In this report, we have identified eight patients having a mutation (C.65G>C), which converts arginine at position 22 to proline (p.Arg22Pro) in the N terminus of FANCG. The mutant protein, hFANCGR22P, is able to repair the DNA and able to retain the monoubiquitination of FANCD2 in the FANCGR22P/FGR22P cell. However, it lost mitochondrial localization and failed to protect mitochondria from oxidative stress. Mitochondrial instability in the FANCGR22P cell causes the transcriptional downregulation of mitochondrial iron-sulfur cluster biogenesis protein frataxin (FXN) and the resulting iron deficiency of FA protein FANCJ, an iron-sulfur-containing helicase involved in DNA repair.