Investigation of molecular details of a bacterial cationic amino acid transporter (GkApcT) during arginine transportation using molecular dynamics simulation and umbrella sampling techniques.

Context: Cationic amino acid transporters (CATs) facilitate arginine transport across membranes and maintain its levels in various tissues and organs, but their overexpression has been associated with severe cancers. A recent study identified the alternating access mechanism and critical residues involved in arginine transportation in a cationic amino acid transporter from Geobacillus kaustophilus (GkApcT). Here, we used molecular dynamics (MD) simulation methods to investigate the transportation mechanism of arginine (Arg) through GkApcT.

Arginine transportation mechanism through cationic amino acid transporter 1: insights from molecular dynamics studies.

Metabolic and signaling mechanisms in mammalian cells are facilitated by the transportation of L-arginine (Arg) across the plasma membrane through cationic amino acid transporter (CAT) proteins. Due to a lack of argininosuccinate synthase (ASS) activity in various tumor cells such as acute myeloid leukemia, acute lymphocytic leukemia, and chronic lymphocytic leukemia, these tumor entities are arginine-auxotrophic and therefore depend on the uptake of the amino acid arginine. Cationic amino acid transporter-1 (CAT-1) is the leading arginine importer expressed in the aforementioned tumor entities.

Therapeutic effects of L-arginine, L-carnitine, and mesenchymal stem cell-conditioned medium on endometriosis-induced oocyte poor quality in an experimental mouse model.

Aim: The present study aimed to explore the potential ameliorative effects of L-arginine (LA), L-carnitine (LC), and bone marrow mesenchymal stem cell-conditioned medium (BMSC-CM) on endometriosis (EMS) model in vivo and in vitro.

Methods: The animals were divided into two main groups, normal and EMS-induced mice. Normal and EMS-induced groups were injected with or without LA (250 mg/kg), LC (250 mg/kg), and BMSC-CM (a final volume of 100 μL of CM/mouse).

LRH-1 (liver receptor homolog-1) derived affinity peptide ligand to inhibit interactions between β-catenin and LRH-1 in pancreatic cancer cells: from computational design to experimental validation.

Poor prognosis, rapid progression and the lack of an effective treatment make pancreatic cancer one of the most lethal malignancies. Recent studies point to a role for liver receptor homolog-1 (LRH-1) in pathogenesis of pancreatic cancer and suggest prevention of the β-catenin/LRH-1 complex formation as a potential strategy for inhibition of the pancreas cancer cells progression. In the current investigation, we have followed a biomimetic strategy and designed an affinity peptide with sequence DEMEEPQQTE to inhibit formation of the β-catenin/LRH-1 complex.

Molecular Basis for Membrane Selectivity of Antimicrobial Peptide Pleurocidin in the Presence of Different Eukaryotic and Prokaryotic Model Membranes.

Pleurocidin, a 25-residue cationic peptide, has antimicrobial activity against bacteria and fungi but exhibits very low hemolytic activity against human red blood cells (RBC). The peptide inserts into the bacterial membrane and causes the membrane to become permeable by either toroidal or carpet mechanism. Herein, to investigate the molecular basis for membrane selectivity of Pleurocidin, the interaction of the peptide with the different membrane models including the RBC, DOPC, DOPC/DOPG (3:1), POPE/POPG (3:1), and POPE/POPG (1:3) bilayers were studied by performing all-atom molecular dynamics (MD) simulation.

Comparative experimental/theoretical studies on the EGFR dimerization under the effect of EGF/EGF analogues binding: Highlighting the importance of EGF/EGFR interactions at site III interface.

Epidermal growth factor receptors (EGFRs) and their cytoplasmic tyrosine kinases play significant roles in cell proliferation and signaling. All the members of the EGFR/ErbB family are primary goals for cancer therapy, particularly for tumors of breast, cervix, ovaries, kidney, esophagus, prostate and non-small-cell lung carcinoma and head and neck tumors. However, the therapeutic ability of accessible anti-ErbB agents is limited.

Enhancement of intrinsic fluorescence of human carbonic anhydrase II upon topiramate binding: Some evidence for drug-induced molecular contraction of the protein.

In this report, the effect of topiramate (TPM), an anticonvulsant sulfamate drug, on the structure of human carbonic anhydrase II (hCA II) was investigated by spectroscopic techniques. The intrinsic fluorescence experiments indicated that TPM binding causes enhancement of enzyme fluorescence via decreasing the internal quenching and energy transfer efficiency, the result supported by molecular dynamics simulation. Thermodynamic analysis of the binding process suggested that hydrogen bonding and van der Waals interactions are the major forces in the interaction of TPM with hCA II.

Comprehensive Dissection of Transcriptome Data and Regulatory Factors in Pancreatic Cancer Cells.

Features of pancreatic cancers include high mortality rates caused by rapid tumor progression and a lack of effective therapy. Underpinning the molecular mechanisms involved in the alteration of the gene expression program in the pancreatic cancer remains to be understood. In the current study, we performed a comprehensive analysis using 282 pancreatic tumor and normal samples from seven independent expression data sets to provide a better view on the interactions between different transcription factors (TFs) and the most affected biological pathways in pancreatic cancer.

Appraisal of role of the polyanionic inducer length on amyloid formation by 412-residue 1N4R Tau protein: A comparative study.

In many neurodegenerative diseases, formation of protein fibrillar aggregates has been observed as a major pathological change. Neurofibrillary tangles, mainly composed of fibrils formed by the microtubule-associated protein; Tau, are a hallmark of a group of neurodegenerative diseases such as Alzheimer's disease. Tau belongs to the class of natively unfolded proteins and partially folds into an ordered β-structure during aggregation.

Spectroscopic and molecular modeling studies on binding of dorzolamide to bovine and human carbonic anhydrase II.

This report is a comparative evaluation on the interaction of dorzolamide (DZA) with bovine and human carbonic anhydrase II (bCA II and hCA II, respectively) using fluorimetry, UV-vis and circular dichroism (CD) spectroscopy as well as molecular docking and molecular dynamics studies. Fluorescence data obtained at different temperatures indicated that DZA quenched the intrinsic fluorescence of both enzymes through a static mechanism. Thermodynamic analysis of the quenching data revealed that hydrogen bonding and van der Waals interactions play important roles in drug binding.

Anti-tumor Activity of Ferulago angulata Boiss. Extract in Gastric Cancer Cell Line via Induction of Apoptosis.

Ferulago angulata Boiss. known in Iran as Chavir, has some bioactive compounds having antioxidant activity. Because of its antioxidant activities, it sounded Chavir extract can be a good candidate for finding chemopreventive agents having inductive apoptosis properties on cancer cells.

Role of CHK2 inhibitors in the cellular responses to ionizing radiation.

Ionizing radiation is the more effective therapy to reduce tumor growth through damaging the DNA of cells. In response to DNA damage, cells activate the checkpoint kinases such as CHK2, which signal to initiate repair processes and cell-cycle arrest, until the damaged DNA is repaired. At present, the development of CHK2 inhibitors has provided an interesting strategy for the treatment of cancer by introducing new radiation modifier agents.

Appraisal of sildenafil binding on the structure and promiscuous esterase activity of native and histidine-modified forms of carbonic anhydrase II.

Sildenafil was investigated for its interaction with the native and modified human carbonic anhydrase II (hCA II). Modification of exposed histidine side chains with diethyl pyrocarbonate decreased esterase activity of the enzyme. The treatment of both native and modified CA with sildenafil revealed slight and moderate enzyme activation profiles, respectively.