المؤلفون: Hamid Hadi-Alijanvand, Ali Akbar Moosavi-Movahedi, Bahram Goliaei

المصدر: Journal of the Iranian Chemical Society. 10:907-914

مصطلحات موضوعية: Angiogenesis, Mechanism (biology), Chemistry, Cell, General Chemistry, Cell biology, Molecular dynamics, medicine.anatomical_structure, Biochemistry, Hypoxia-inducible factors, Cancer cell, Unfolded protein response, medicine, Gene

الوصف: Prolyl hydroxylase domain 2 containing protein (PHD2) is a central protein in regulation of cellular response to hypoxia. This protein controls the responses of cell to oxygen level via the regulation of hypoxia inducible factor (HIF) stability. HIF induces the expression of many genes, especially ones orchestrate angiogenesis. There are some reports that mentioned in some tumor types the level of HIF is high in spite of the presence of wild-type PHD2 and normoxic environment. Therefore, the possibility of PHD2 misfolding in some cancer cells arises. Studying such important protein unfolding pathway is insightful for possible therapeutic approaches. In this study, the unfolding pathway of PHD2 illustrates utilizing molecular dynamics simulation of protein thermal denaturation. Based on current study results, we represent the possible mechanisms of PHD2 unfolding in detail. The possible intermediates of PHD2 thermal unfolding are characterized, and the most venomous state of its unfolding pathway is introduced.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::6a04ec0868a5b1c7cec994dbb8e65cb8Test
https://doi.org/10.1007/s13738-013-0227-3Test

المؤلفون: Gholam Hossein Riazi, Roya Mahinpour, Shahin Ahmadian, Zahra Naghdi Gheshlaghi, Hamid Hadi Alijanvand, Mohammad N. Sarbolouki, Kayhan Azadmanesh, Ali Akbar Moosavi-Movahedi, Masoumeh Douraghi, Maryam Kavousi Heidari, Mohammad Ali Shokrgozar

المصدر: Cell Biology International. 36:403-408

مصطلحات موضوعية: Models, Molecular, Tetrazolium Salts, Apoptosis, Microtubules, Arsenicals, Polymerization, Microtubule polymerization, HeLa, Microscopy, Electron, Transmission, Tubulin, Microtubule, In Situ Nick-End Labeling, Animals, Humans, Cell Proliferation, Binding Sites, Sheep, biology, Tissue Extracts, Cell growth, Tubulin Modulators, Brain, Cell Biology, General Medicine, Fibroblasts, biology.organism_classification, In vitro, Cell biology, Thiazoles, Cancer cell, biology.protein, HeLa Cells, Protein Binding

الوصف: Arsenical compounds exhibit a differential toxicity to cancer cells. Microtubules are a primary target of a number of anticancer drugs, such as arsenical compounds. The interaction of 1-NAA (1-naphthylarsonic acid) has been investigated on microtubule polymerization under in vitro and cellular conditions. Microtubules were extracted from sheep brain. Transmission electron microscopy was used to show microtubule structure in the presence of 1-NAA. Computational docking method was applied for the discovery of ligand-binding sites on the microtubular proteins. Proliferation of HeLa cells and HF2 (human foreskin fibroblasts) was measured by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay method following their incubation with 1-NAA. Fluorescence microscopic labelling was done with the help of α-tubulin monoclonal antibody and Tunel kit was used to investigate the apoptotic effects of 1-NAA on the HeLa cells. 1-NAA inhibits the tubulin polymerization by the formation of abnormal polymers having high affinity to the inner cell wall.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::71befa92cdf52bc05ea9acf20f66595fTest
https://doi.org/10.1042/cbi20100603Test

المؤلفون: Fariba Khodagholi, Mahmoud Kiaei, Niloufar Ansari, Marjan Sabbaghian, Hamid Hadi-Alijanvand

المصدر: Journal of biomolecular structuredynamics. 32(8)

مصطلحات موضوعية: Boron Compounds, Models, Molecular, Molecular Sequence Data, Apoptosis, Biology, PC12 Cells, Dantrolene, Structural Biology, medicine, Autophagy, Animals, Inositol 1,4,5-Trisphosphate Receptors, Amino Acid Sequence, Receptor, Molecular Biology, Neurons, Voltage-dependent calcium channel, Sequence Homology, Amino Acid, Ryanodine receptor, Triazines, Endoplasmic reticulum, Ryanodine Receptor Calcium Release Channel, General Medicine, Hydrogen Peroxide, Calcium Channel Blockers, Endoplasmic Reticulum Stress, Cell biology, Rats, Neuroprotective Agents, Cell culture, Second messenger system, Unfolded protein response, Calcium, medicine.drug, Signal Transduction

الوصف: Ca(2+) is an essential second messenger, playing a fundamental role in maintaining cell viability and neuronal activity. Two specific endoplasmic reticulum calcium channels, ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs) play an important role in Ca(2+) regulation. In the present study, we provided a 3D structure of RyR and IP3R by homology modeling, and we predicted their interactions with a known neuroprotective compound, 3-thiomethyl-5,6-(dimethoxyphenyl)-1,2,4-triazine (TDMT), as well as two inhibitors, dantrolene and 2-aminoethoxydiphenyl borate (2-APB). Interestingly, we found that dantrolene and 2-APB can bind to the IP3-binding domain of IP3R and RyR, while TDMT may directly block both channels by interacting with the putative resident domains in the pore. Cell culture experiments showed that these compounds could protect PC12 cells against H2O2-induced apoptosis and activate autophagic pathways. Collectively, our computational (in silico) and cell culture studies suggest that RyR and IP3R are novel and promising targets to be used against neurodegenerative diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a1d838a624d6ec85cf4a0c757e4b28bTest
https://pubmed.ncbi.nlm.nih.gov/23829337Test

المؤلفون: Nikolay V. Dokholyan, Hamid Hadi-Alijanvand, Bahram Goliaei, Ali Akbar Moosavi-Movahedi, Elizabeth A. Proctor

المصدر: PLoS ONE, Vol 7, Iss 10, p e47061 (2012)
PLoS ONE

مصطلحات موضوعية: Protein Folding, Protein Structure, Angiogenesis, Procollagen-Proline Dioxygenase, Biophysics, lcsh:Medicine, Biology, Molecular Dynamics Simulation, Molecular Dynamics, Biochemistry, Biophysics Simulations, Metastasis, Hypoxia-Inducible Factor-Proline Dioxygenases, Protein structure, Computational Chemistry, Catalytic Domain, Molecular Cell Biology, medicine, Macromolecular Structure Analysis, Humans, lcsh:Science, Protein Unfolding, Genetics, Multidisciplinary, Physics, lcsh:R, Wild type, Temperature, Proteins, Computational Biology, medicine.disease, Cell biology, Regulatory Proteins, Chemistry, Unfolded protein response, Protein folding, lcsh:Q, Procollagen-proline dioxygenase, Function (biology), Research Article

الوصف: Prolyl hydroxylase domain 2 containing protein (PHD2) is a key protein in regulation of angiogenesis and metastasis. In normoxic condition, PHD2 triggers the degradation of hypoxia-inducible factor 1 (HIF-1α) that induces the expression of hypoxia response genes. Therefore the correct function of PHD2 would inhibit angiogenesis and consequent metastasis of tumor cells in normoxic condition. PHD2 mutations were reported in some common cancers. However, high levels of HIF-1α protein were observed even in normoxic metastatic tumors with normal expression of wild type PHD2. PHD2 malfunctions due to protein misfolding may be the underlying reason of metastasis and invasion in such cases. In this study, we scrutinize the unfolding pathways of the PHD2 catalytic domain’s possible species and demonstrate the properties of their unfolding states by computational approaches. Our study introduces the possibility of aggregation disaster for the prominent species of PHD2 during its partial unfolding. This may justify PHD2 inability to regulate HIF-1α level in some normoxic tumor types.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91b7eeffa84469bb831f566423dba24aTest

المؤلفون: Elizabeth A. Proctor, Maryam Rouhani, Hamid Hadi-Alijanvand, Ali Akbar Moosavi-Movahedi, Nikolay V. Dokholyan

المصدر: PLoS ONE
PLoS ONE, Vol 6, Iss 3, p e16778 (2011)

مصطلحات موضوعية: Protein Folding, Protein Structure, Biophysics, lcsh:Medicine, Computational biology, Biology, Receptors, N-Methyl-D-Aspartate, Protein Structure, Secondary, Molecular Cell Biology, Macromolecular Structure Analysis, Animals, Humans, Receptors, AMPA, lcsh:Science, Databases, Protein, Multidisciplinary, Voltage-dependent calcium channel, lcsh:R, Colocalization, Computational Biology, Membrane Proteins, Protein subcellular localization prediction, Transport protein, Cell biology, Folding (chemistry), Protein Transport, Membrane, Eukaryotic Cells, Membrane protein, Prokaryotic Cells, Protein folding, lcsh:Q, Membranes and Sorting, Calcium Channels, Sequence Analysis, Research Article

الوصف: While various approaches exist to study protein localization, it is still a challenge to predict where proteins localize. Here, we consider a mechanistic viewpoint for membrane localization. Taking into account the steps for the folding pathway of α-helical membrane proteins and relating biophysical parameters to each of these steps, we create a score capable of predicting the propensity for membrane localization and call it FP(3)mem. This score is driven from the principal component analysis (PCA) of the biophysical parameters related to membrane localization. FP(3)mem allows us to rationalize the colocalization of a number of channel proteins with the Cav1.2 channel by their fewer propensities for membrane localization.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::05bd7a8c66ca6150b70ef66afcef1eb5Test
http://europepmc.org/articles/PMC3046963Test