keyword
MENU ▼
Read by QxMD icon Read
search

molecular chaperone

keyword
https://www.readbyqxmd.com/read/28221352/dynamic-undocking-and-the-quasi-bound-state-as-tools-for-drug-discovery
#1
Sergio Ruiz-Carmona, Peter Schmidtke, F Javier Luque, Lisa Baker, Natalia Matassova, Ben Davis, Stephen Roughley, James Murray, Rod Hubbard, Xavier Barril
There is a pressing need for new technologies that improve the efficacy and efficiency of drug discovery. Structure-based methods have contributed towards this goal but they focus on predicting the binding affinity of protein-ligand complexes, which is notoriously difficult. We adopt an alternative approach that evaluates structural, rather than thermodynamic, stability. As bioactive molecules present a static binding mode, we devised dynamic undocking (DUck), a fast computational method to calculate the work necessary to reach a quasi-bound state at which the ligand has just broken the most important native contact with the receptor...
March 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28220688/the-dnaj-protein-osdja6-negatively-regulates-rice-innate-immunity-to-the-blast-fungus-magnaporthe-oryzae
#2
Xionghui Zhong, Jiuxia Yang, Yanlong Shi, Xuli Wang, Guo-Liang Wang
Rice blast, caused by Magnaporthe oryzae (synonym: Pyricularia oryzae), severely reduces rice production and grain quality. The molecular mechanism of rice resistance to M. oryzae is not fully understood. In the present study, we identified a chaperone DnaJ protein, OsDjA6, that is involved in basal resistance to M. oryzae in rice. The OsDjA6 protein is distributed in the entire rice cell. The expression of OsDjA6 is significantly induced in rice after infection with a compatible isolate. Silencing of OsDjA6 in transgenic rice enhances resistance to M...
February 21, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28218749/mechanistic-basis-for-the-recognition-of-a-misfolded-protein-by-the-molecular-chaperone-hsp90
#3
Javier Oroz, Jin Hae Kim, Bliss J Chang, Markus Zweckstetter
The critical toxic species in over 40 human diseases are misfolded proteins. Their interaction with molecular chaperones such as Hsp90, which preferentially interacts with metastable proteins, is essential for the blocking of disease progression. Here we used nuclear magnetic resonance (NMR) spectroscopy to determine the three-dimensional structure of the misfolded cytotoxic monomer of the amyloidogenic human protein transthyretin, which is characterized by the release of the C-terminal β-strand and perturbations of the A-B loop...
February 20, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28218284/proteomic-analysis-of-exported-chaperone-co-chaperone-complexes-of-p-falciparum-reveals-an-array-of-complex-protein-protein-interactions
#4
Qi Zhang, Cheng Ma, Alexander Oberli, Astrid Zinz, Sonja Engels, Jude M Przyborski
Malaria parasites modify their human host cell, the mature erythrocyte. This modification is mediated by a large number of parasite proteins that are exported to the host cell, and is also the underlying cause for the pathology caused by malaria infection. Amongst these proteins are many Hsp40 co-chaperones, and a single Hsp70. These proteins have been implicated in several processes in the host cell, including a potential role in protein transport, however the further molecular players in this process remain obscure...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216424/an-atypical-thioredoxin-imparts-early-resistance-to-sugarcane-mosaic-virus-in-maize
#5
Qingqing Liu, Huanhuan Liu, Yangqing Gong, Yongfu Tao, Lu Jiang, Weiliang Zuo, Qin Yang, Jianrong Ye, Jinsheng Lai, Jianyu Wu, Thomas Lübberstedt, Mingliang Xu
Sugarcane mosaic virus (SCMV) disease causes substantial losses of grain yield and forage biomass in susceptible maize worldwide. A major quantitative trait locus, Scmv1, has been identified to impart strong resistance to SCMV at early infection stage. Here, we demonstrate that ZmTrxh, encoding an atypical h-type thioredoxin, is the causal gene at Scmv1, and that its transcript abundance correlated strongly with maize resistance to SCMV. ZmTrxh alleles, whether they are resistant or susceptible, share the identical coding/proximal promoter regions, but vary in the upstream regulatory regions...
February 12, 2017: Molecular Plant
https://www.readbyqxmd.com/read/28214672/evaluation-of-molecular-chaperone-drug-function-regorafenib-and-%C3%AE-cyclodextrins
#6
Xiurong Hu, Mengying Sun, Yang Li, Guping Tang
Regorafenib (RG) was an oral multi-kinase inhibitor with poor water solubility. In order to enhance the drug's solubility, dissolution and bioavailability, the binary molecular chaperone drug between RG and β-cyclodetrin (β-CD) had prepared by co-crystallization. The structure of RG-β-CD was characterized by thermal analysis, powder X-ray diffraction, infrared spectroscopy and nuclear magnetic resonance. Phase-solubility study revealed the higher solubility and complexing ability of β-CDwith RG.The solubility and dissolution of RG-β-CD was significantly enhanced in pH 1...
February 7, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28214555/identification-of-a-fatty-acid-binding-protein4-ucp2-axis-regulating-microglial-mediated-neuroinflammation
#7
Cayla M Duffy, Hongliang Xu, Joshua P Nixon, David A Bernlohr, Tammy A Butterick
Hypothalamic inflammation contributes to metabolic dysregulation and the onset of obesity. Dietary saturated fats activate microglia via a nuclear factor-kappa B (NFκB) mediated pathway to release pro-inflammatory cytokines resulting in dysfunction or death of surrounding neurons. Fatty acid binding proteins (FABPs) are lipid chaperones regulating metabolic and inflammatory pathways in response to fatty acids. Loss of FABP4 in peripheral macrophages via either molecular or pharmacologic mechanisms results in reduced obesity-induced inflammation via a UCP2-redox based mechanism...
February 15, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28213157/presynaptic-protein-homeostasis-and-neuronal-function
#8
REVIEW
Yu-Chun Wang, Elsa Lauwers, Patrik Verstreken
Proteome integrity is maintained by a coordinated network of molecular chaperones, by protein degradation machineries and by their regulators. Numerous human pathologies are considered as diseases of compromised protein homeostasis (proteostasis), including neurodegeneration. These are characterized by the accumulation of neuronal protein aggregates and by synaptic defects followed by loss of connectivity and cell death. While this suggests that synaptic terminals are particularly sensitive to proteostasis imbalance, our understanding of protein turnover mechanisms and regulation at the synapse remains limited...
February 14, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28212901/the-dissociation-of-the-hsp60-pro-caspase-3-complex-by-bis-pyridyl-oxadiazole-copper-complex-cubipyoxa-leads-to-cell-death-in-nci-h292-cancer-cells
#9
Celeste Caruso Bavisotto, Dragana Nikolic, Antonella Marino Gammazza, Rosario Barone, Filippa Lo Cascio, Emanuele Mocciaro, Giovanni Zummo, Everly Conway de Macario, Alberto Jl Macario, Francesco Cappello, Valentina Giacalone, Andrea Pace, Giampaolo Barone, Antonio Palumbo Piccionello, Claudia Campanella
Cell survival and proliferation are central to carcinogenesis, involving various mechanisms among which those that impede apoptosis are important. In this, the role of the molecular chaperone Hsp60 is unclear since it has been reported that it can be both, pro- or anti-apoptotic. A solution to this riddle is crucial to the development of anti-cancer therapies targeting Hsp60. We addressed this question using a tumor cell line, NCI-H292, and [Cu(3,5-bis(2'-pyridyl)-1,2,4-oxadiazole)2(H2O)2](ClO4)2, CubipyOXA, a copper-containing compound with cytotoxic properties...
February 10, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28211870/non-apoptotic-functions-of-caspases-in-myeloid-cell-differentiation
#10
REVIEW
Stéphanie Solier, Michaela Fontenay, William Vainchenker, Nathalie Droin, Eric Solary
Subtle caspase activation is associated with the differentiation of several myeloid lineages. A tightly orchestrated dance between caspase-3 activation and the chaperone HSP70 that migrates to the nucleus to protect the master regulator GATA-1 from cleavage transiently occurs in basophilic erythroblasts and may prepare nucleus and organelle expel that occurs at the terminal phase of erythroid differentiation. A spatially restricted activation of caspase-3 occurs in maturing megakaryocytes to promote proplatelet maturation and platelet shedding in the bloodstream...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28203481/lens-endogenous-peptide-%C3%AE-a66-80-generates-hydrogen-peroxide-and-induces-cell-apoptosis
#11
Murugesan Raju, Puttur Santhoshkumar, K Krishna Sharma
In previous studies, we reported the presence of a large number of low-molecular-weight (LMW) peptides in aged and cataract human lens tissues. Among the LMW peptides, a peptide derived from αA-crystallin, αA66-80, was found in higher concentration in aged and cataract lenses. Additional characterization of the αA66-80 peptide showed beta sheet signature, and it formed well-defined unbranched fibrils. Further experimental data showed that αA66-80 peptide binds α-crystallin, impairs its chaperone function, and attracts additional crystallin proteins to the peptide α-crystallin complex, leading to the formation of larger light scattering aggregates...
February 2017: Aging and Disease
https://www.readbyqxmd.com/read/28203225/regulation-of-sterol-biosynthesis-in-the-human-fungal-pathogen-aspergillus-fumigatus-opportunities-for-therapeutic-development
#12
REVIEW
Sourabh Dhingra, Robert A Cramer
Sterols are a major component of eukaryotic cell membranes. For human fungal infections caused by the filamentous fungus Aspergillus fumigatus, antifungal drugs that target sterol biosynthesis and/or function remain the standard of care. Yet, an understanding of A. fumigatus sterol biosynthesis regulatory mechanisms remains an under developed therapeutic target. The critical role of sterol biosynthesis regulation and its interactions with clinically relevant azole drugs is highlighted by the basic helix loop helix (bHLH) class of transcription factors known as Sterol Regulatory Element Binding Proteins (SREBPs)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28202679/from-molecular-chaperones-to-membrane-motors-through-the-lens-of-a-mass-spectrometrist
#13
REVIEW
Carol V Robinson
Twenty-five years ago, we obtained our first mass spectra of molecular chaperones in complex with protein ligands and entered a new field of gas-phase structural biology. It is perhaps now time to pause and reflect, and to ask how many of our initial structure predictions and models derived from mass spectrometry (MS) datasets were correct. With recent advances in structure determination, many of the most challenging complexes that we studied over the years have become tractable by other structural biology approaches enabling such comparisons to be made...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28201527/high-dose-of-antibiotic-colistin-induces-oligomerization-of-molecular-chaperone-hsp90
#14
Shuntaro Togashi, Kyosuke Takahashi, Arisa Tamura, Ikumi Toyota, Shiori Hatakeyama, Atsushi Komatsuda, Ikuru Kudo, Erina Sasaki Kudoh, Tomoya Okamoto, Asami Haga, Asuka Miyamoto, Ewa Grave, Taku Sugawara, Hiroaki Shimizu, Hideaki Itoh
No abstract text is available yet for this article.
February 14, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28199839/the-survival-of-motor-neuron-protein-acts-as-a-molecular-chaperone-for-mrnp-assembly
#15
Paul G Donlin-Asp, Claudia Fallini, Jazmin Campos, Ching-Chieh Chou, Megan E Merritt, Han C Phan, Gary J Bassell, Wilfried Rossoll
Spinal muscular atrophy (SMA) is a motor neuron disease caused by reduced levels of the survival of motor neuron (SMN) protein. SMN is part of a multiprotein complex that facilitates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). SMN has also been found to associate with mRNA-binding proteins, but the nature of this association was unknown. Here, we have employed a combination of biochemical and advanced imaging methods to demonstrate that SMN promotes the molecular interaction between IMP1 protein and the 3' UTR zipcode region of β-actin mRNA, leading to assembly of messenger ribonucleoprotein (mRNP) complexes that associate with the cytoskeleton to facilitate trafficking...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28192191/the-crystal-structure-of-the-hsp90-co-chaperone-cpr7-from-saccharomyces-cerevisiae
#16
Yu Qiu, Qiangqiang Ge, Mingxing Wang, Hui Lv, Mohammad Ebrahimi, Liwen Niu, Maikun Teng, Xu Li
The versatility of Hsp90 can be attributed to the variety of co-chaperone proteins that modulate the role of Hsp90 in many cellular processes. As a co-chaperone of Hsp90, Cpr7 is essential for accelerating the cell growth in an Hsp90-containing trimeric complex. Here, we report the crystal structure of Cpr7 at a resolution of 1.8Å. It consists of an N-terminal PPI domain and a C-terminal TPR domain, and exhibits a U-shape conformation. Our studies revealed the aggregation state of Cpr7 in solution and the interaction properties between Cpr7 and the MEEVD sequence from the C-terminus of Hsp90...
February 9, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28190459/mutations-in-inpp5k-cause-a-form-of-congenital-muscular-dystrophy-overlapping-marinesco-sj%C3%A3-gren-syndrome-and-dystroglycanopathy
#17
Daniel P S Osborn, Heather L Pond, Neda Mazaheri, Jeremy Dejardin, Christopher J Munn, Khaloob Mushref, Edmund S Cauley, Isabella Moroni, Maria Barbara Pasanisi, Elizabeth A Sellars, R Sean Hill, Jennifer N Partlow, Rebecca K Willaert, Jaipreet Bharj, Reza Azizi Malamiri, Hamid Galehdari, Gholamreza Shariati, Reza Maroofian, Marina Mora, Laura E Swan, Thomas Voit, Francesco J Conti, Yalda Jamshidi, M Chiara Manzini
Congenital muscular dystrophies display a wide phenotypic and genetic heterogeneity. The combination of clinical, biochemical, and molecular genetic findings must be considered to obtain the precise diagnosis and provide appropriate genetic counselling. Here we report five individuals from four families presenting with variable clinical features including muscular dystrophy with a reduction in dystroglycan glycosylation, short stature, intellectual disability, and cataracts, overlapping both the dystroglycanopathies and Marinesco-Sjögren syndrome...
February 1, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28179395/molecular-physiology-of-freeze-tolerance-in-vertebrates
#18
REVIEW
Kenneth B Storey, Janet M Storey
Freeze tolerance is an amazing winter survival strategy used by various amphibians and reptiles living in seasonally cold environments. These animals may spend weeks or months with up to ∼65% of their total body water frozen as extracellular ice and no physiological vital signs, and yet after thawing they return to normal life within a few hours. Two main principles of animal freeze tolerance have received much attention: the production of high concentrations of organic osmolytes (glucose, glycerol, urea among amphibians) that protect the intracellular environment, and the control of ice within the body (the first putative ice-binding protein in a frog was recently identified), but many other strategies of biochemical adaptation also contribute to freezing survival...
April 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28178571/genome-wide-identification-and-analysis-of-biotic-and-abiotic-stress-regulation-of-small-heat-shock-protein-hsp20-family-genes-in-bread-wheat
#19
Senthilkumar K Muthusamy, Monika Dalal, Viswanathan Chinnusamy, Kailash C Bansal
Small Heat Shock Proteins (sHSPs)/HSP20 are molecular chaperones that protect plants by preventing protein aggregation during abiotic stress conditions, especially heat stress. Due to global climate change, high temperature is emerging as a major threat to wheat productivity. Thus, the identification of HSP20 and analysis of HSP transcriptional regulation under different abiotic stresses in wheat would help in understanding the role of these proteins in abiotic stress tolerance. We used sequences of known rice and Arabidopsis HSP20 HMM profiles as queries against publicly available wheat genome and wheat full length cDNA databases (TriFLDB) to identify the respective orthologues from wheat...
January 22, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28177905/trap1-protein-signature-predicts-outcome-in-human-metastatic-colorectal-carcinoma
#20
Francesca Maddalena, Vittorio Simeon, Giulia Vita, Annamaria Bochicchio, Luciana Possidente, Lorenza Sisinni, Giacomo Lettini, Valentina Condelli, Danilo Swann Matassa, Valeria Li Bergolis, Alberto Fersini, Sante Romito, Michele Aieta, Antonio Ambrosi, Franca Esposito, Matteo Landriscina
TRAP1 is a HSP90 molecular chaperone upregulated in colorectal carcinomas and involved in control of intracellular signaling, cell cycle, apoptosis and drug resistance, stemness and bioenergetics through co-traslational regulation of a network of client proteins. Thus, the clinical significance of TRAP1 protein network was analyzed in human colorectal cancers. TRAP1 and/or its client proteins were quantified, by immunoblot analysis, in 60 surgical specimens of colorectal carcinomas at different stages and, by immunohistochemistry, in 9 colorectal adenomatous polyps, 11 in situ carcinomas and 55 metastatic colorectal tumors...
February 3, 2017: Oncotarget
keyword
keyword
76712
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"