Articles

Structure and Substrate Recognition of the Escherichia coli Transport Protein NupG from the Nucleoside: H+ Symporter (NHS) Family

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The nucleoside transporter NupG is one of the two principal transport proteins in the inner membrane of Escherichia coli that enable the organism to scavenge nucleosides from its external environment. NupG functions in a symport manner driven by the proton motive force and is a member of the Nucleoside:H+ Symporter (NHS) subfamily of the Major Facilitator Superfamily (MFS) of transporters. NupG has broad substrate specificity, transporting all naturally occurring purine and pyrimidine nucleosides. In studies over many years the nupG gene has been cloned and amplified, and the NupG protein has been purified, subjected to biochemical, biophysical and computational analysis, and its X-ray structure determined in the apo state at 3.0 Å resolution. The NupG structure had a typical MFS fold with twelve transmembrane spanning α-helices and distinct N- and C-terminal domains linked by a flexible loop. Preliminary site-directed mutagenesis and molecular docking studies on NupG identified nine putative nucleoside binding pocket residues (R136, T140, F143, Q225, N228, Q261, E264, Y318, F322) and a mutant (D323A) with 20-fold enhanced uridine binding activity. Further biochemical and structural investigations are necessary to better understand the substrate recognition and molecular mechanism of E. coli NHS family proteins (NupG, XapB, YegT).

Investigation of Momordica charantia phytochemicals against PIM1 Kinase: A Computational Approach

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Prostate cancer is a significant contributor to male cancer-related mortality. PIM1 kinase has implications in the development and progression of various cancers, particularly prostate cancer. PIM1, a serine/threonine protein kinase plays a crucial role in cellular processes including survival, growth and differentiation. In prostate cancer increased PIM1 expression is associated with a more aggressive phenotype and poorer patient outcomes. It has emerged as a promising therapeutic target for prostate cancer treatment. The development of PIM1 kinase inhibitors has greatly enhanced and progressed significantly. Different stages of clinical trials demonstrating their potential as therapeutic agents. Momordica charantia, or bitter melon has a long history in traditional medicine for various health conditions, it is very rich in secondary metabolites like triterpenoids, glycosides, alkaloids, flavonoids and phenolic acids. Bitter melon is considered to have medicinal properties including potential anticancer phytochemicals. This study employs virtual screening, molecular dynamic simulation and ADME/T analysis to explore bitter melon’s phytochemicals and their interaction with PIM1 kinase. The goal is to understand the molecular details and pharmacokinetics of bitter melon compounds evaluating their potential as therapeutic agents against prostate cancer. In our present study, it was found that out of all investigated phytochemicals catechin and gallic acid shows satisfactory result depending upon various parameters taken into consideration for conducting the study.

Potential of Aloin B Compound and its Derivatives as Type-2 Antidiabetic

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Type-2 diabetes mellitus occurs due to suboptimal insulin function (insulin resistance) or decreased insulin function. Type-2 diabetes mellitus treatment is chronic and lifelong. One of the treatments is the use of insulin and oral anti-diabetic drugs. This treatment requires a long period of time and can cause unwanted side effects. Therefore, alternative treatments are needed with minimal side effects by utilizing herbal plants containing Aloin B compounds because they have been proven to be used as antidiabetic agents. These compounds can be found from the Aloe Vera plant (Aloe Vera l.). The aim of this study was to find compounds derived from Aloin B compounds that have the most potential as anti-diabetic type-2 by inhibiting the pancreatic α-amylase enzyme (code: 1B2Y) in breaking down starch in the body. The certainty of the presence of the compound Aloin B in the flesh of the aloe plant was confirmed by the LC-MS test. This research was conducted using the Quantitative Structure-Activity Relationship (QSAR) and Molecular Bonding method. The results showed that the ID S22 compound with the IUPAC name (S)-10-amino-1,2,8-trihydroxy-6- (hydroxymethyl) -10- ((2R,3R,4S,5S,6R) -2,3, 4,5-tetrahydroxy–6(hydroxymethyl) tetrahydro-2H-piran-2-yl) anthracene-9(10H)-one is the most potent compound from Aloin B derivatives as a type-2 antidiabetic agent in the mechanism of inhibiting α-enzyme action pancreatic amylase, based on the value of R2 = 0.980, the PRESS value of the compound was 0.0004, the binding energy value was -7.07 kcal/mol, the inhibition constant was 6.58 uM and the formation of hydrogen bonds between the compound and the amino acid residues aspirin, glycine, threonine and arginine.

Potencial of Ursolic Acid Derivatives as Anti Breast Cancer

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Breast cancer is one of the biggest contributors to death in the world. Several treatment methods such as chemotherapy, hormonal therapy, radiation therapy, and surgery have shown side effects and resistance to breast cancer. Bioactive compounds are now an alternative in the development of drugs for breast cancer. Pearl grass is one of the plants reported to contain bioactive compounds that have inhibitory activity against breast cancer cells, namely ursolic acid. Most reports describe modifications of groups on its structure increasing the potential of ursolic acid as a breast cancer drug. This study aims to develop breast cancer drugs with raw materials of ursolic acid derivative compounds that are modified on the active side with groups that play an important role as anticancer using the Quantitative Structure and Activity Relationship (QSAR) method and molecular docking. The QSAR descriptors used are hydrophobic, steric, and electronic. The characters of each descriptor were computed using the SwissADME, Molinspiration, and NWChem programs with the DFT method, B3LYP function, and 6-31G* basis set. Molecular docking was performed using the AutoDock Tools 1.5.6 program and visualized using the Biovia Studio Visualizer program. The results showed that the regression coefficient (R2) of the QSAR model had a high correlation of 0.985 with the compound (1S,2R,4aS,6aR,6bR,10S,12aR,12bR,14bS)-10-amino-1,2,6a,6b,9,9, 12a-heptamethyl-14-oxoicosahydropicene-4a(2H)-carboxylic acid became the best compound validated by the results of molecular docking which has a binding energy of -7.92 kcal/mol and an inhibition constant of 1.42 nM so that it can inhibit MCF-7 cells in breast cancer.