Protein structure could unlock new treatments for cystic fibrosis
(University of Zurich) Biochemists at the University of Zurich have used cryo-electron microscopy to determine the detailed architecture of the chloride channel TMEM16A. This protein is a promising target for the development of effective drugs to treat cystic fibrosis. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - December 13, 2017 Category: International Medicine & Public Health Source Type: news
Bacteria breakthrough marks new era in cellular design and biofuel production
Scientists at the universities of Kent and Bristol have built a miniature scaffold inside bacteria that can bolster cellular productivity, providing the foundation for a new era of cellular protein engineering and biofuel production. (Source: University of Bristol news)
Source: University of Bristol news - December 11, 2017 Category: Universities & Medical Training Tags: International, Public engagement, Research; Faculty of Biomedical Sciences, Faculty of Biomedical Sciences, School of Biochemistry, Institutes, Bristol BioDesign Institute Source Type: news
A spring-loaded sensor for cholesterol in cells
(American Society for Biochemistry and Molecular Biology) New research from the University of New South Wales in Sydney, Australia, to be published in the Journal of Biological Chemistry on Dec. 8, explains how an enzyme acts as a kind of thermostat that responds to and adjusts levels of cholesterol in the cell. This insight could lead to new strategies for combating high cholesterol. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - December 7, 2017 Category: Biology Source Type: news
Structural basis for methylphosphonate biosynthesis
Methylphosphonate synthase (MPnS) produces methylphosphonate, a metabolic precursor to methane in the upper ocean. Here, we determine a 2.35-angstrom resolution structure of MPnS and discover that it has an unusual 2-histidine-1-glutamine iron-coordinating triad. We further solve the structure of a related enzyme, hydroxyethylphosphonate dioxygenase from Streptomyces albus (SaHEPD), and find that it displays the same motif. SaHEPD can be converted into an MPnS by mutation of glutamine-adjacent residues, identifying the molecular requirements for methylphosphonate synthesis. Using these sequence markers, we find numerous pu...
Source: ScienceNOW - December 7, 2017 Category: Science Authors: Born, D. A., Ulrich, E. C., Ju, K.-S., Peck, S. C., van der Donk, W. A., Drennan, C. L. Tags: Biochemistry reports Source Type: news
Postcatalytic spliceosome structure reveals mechanism of 3'-splice site selection
Introns are removed from eukaryotic messenger RNA precursors by the spliceosome in two transesterification reactions—branching and exon ligation. The mechanism of 3'–splice site recognition during exon ligation has remained unclear. Here we present the 3.7-angstrom cryo–electron microscopy structure of the yeast P-complex spliceosome immediately after exon ligation. The 3'–splice site AG dinucleotide is recognized through non–Watson-Crick pairing with the 5' splice site and the branch-point adenosine. After the branching reaction, protein factors work together to remodel the spliceosome and st...
Source: ScienceNOW - December 7, 2017 Category: Science Authors: Wilkinson, M. E., Fica, S. M., Galej, W. P., Norman, C. M., Newman, A. J., Nagai, K. Tags: Biochemistry, Molecular Biology r-articles Source Type: news
Structure of the yeast spliceosomal postcatalytic P complex
The spliceosome undergoes dramatic changes in a splicing cycle. Structures of B, Bact, C, C*, and intron lariat spliceosome complexes revealed mechanisms of 5'–splice site (ss) recognition, branching, and intron release, but lacked information on 3'-ss recognition, exon ligation, and exon release. Here we report a cryo–electron microscopy structure of the postcatalytic P complex at 3.3-angstrom resolution, revealing that the 3' ss is mainly recognized through non–Watson-Crick base pairing with the 5' ss and branch point. Furthermore, one or more unidentified proteins become stably associated with the P co...
Source: ScienceNOW - December 7, 2017 Category: Science Authors: Liu, S., Li, X., Zhang, L., Jiang, J., Hill, R. C., Cui, Y., Hansen, K. C., Zhou, Z. H., Zhao, R. Tags: Biochemistry r-articles Source Type: news
Plant RuBisCo assembly in E. coli with five chloroplast chaperones including BSD2
Plant RuBisCo, a complex of eight large and eight small subunits, catalyzes the fixation of CO2 in photosynthesis. The low catalytic efficiency of RuBisCo provides strong motivation to reengineer the enzyme with the goal of increasing crop yields. However, genetic manipulation has been hampered by the failure to express plant RuBisCo in a bacterial host. We achieved the functional expression of Arabidopsis thaliana RuBisCo in Escherichia coli by coexpressing multiple chloroplast chaperones. These include the chaperonins Cpn60/Cpn20, RuBisCo accumulation factors 1 and 2, RbcX, and bundle-sheath defective-2 (BSD2). Our struc...
Source: ScienceNOW - December 7, 2017 Category: Science Authors: Aigner, H., Wilson, R. H., Bracher, A., Calisse, L., Bhat, J. Y., Hartl, F. U., Hayer-Hartl, M. Tags: Biochemistry r-articles Source Type: news
Putting the RuBisCO pieces together
Source: ScienceNOW - December 7, 2017 Category: Science Authors: Yeates, T. O., Wheatley, N. M. Tags: Biochemistry perspective Source Type: news
The Dream Chemistry Award goes to Dr. Jessica R. Kramer from the University of Utah
(Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague)) The laureate of the Dream Chemistry Award 2017 became Dr. Jessica R. Kramer from the University of Utah, USA, nominated by Prof. Hamid Ghandehari, with a project 'Glycocalyx engineering to probe the role of mucins in cancer'. (Source: EurekAlert! - Cancer)
Source: EurekAlert! - Cancer - December 6, 2017 Category: Cancer & Oncology Source Type: news
3.9 A structure of the yeast Mec1-Ddc2 complex, a homolog of human ATR-ATRIP
The ataxia telangiectasia–mutated and Rad3-related (ATR) kinase is a master regulator of DNA damage response and replication stress in humans, but the mechanism of its activation remains unclear. ATR acts together with its partner ATRIP. Using cryo–electron microscopy, we determined the structure of intact Mec1-Ddc2 (the yeast homolog of ATR-ATRIP), which is poised for catalysis, at a resolution of 3.9 angstroms. Mec1-Ddc2 forms a dimer of heterodimers through the PRD and FAT domains of Mec1 and the coiled-coil domain of Ddc2. The PRD and Bridge domains in Mec1 constitute critical regulatory sites. The activati...
Source: ScienceNOW - November 30, 2017 Category: Science Authors: Wang, X., Ran, T., Zhang, X., Xin, J., Zhang, Z., Wu, T., Wang, W., Cai, G. Tags: Biochemistry, Molecular Biology reports Source Type: news
Alan Eddy obituary
My father, Alan Eddy, who has died aged 90, was the founding professor of biochemistry at Umist - the University of Manchester Institute of Science and Technology – where he carried out groundbreaking work with yeast. He was appointed professor and head of the department of biochemistry in 1959, and was in the vanguard of Umist’s transformation into a leading university.Born in St Just, Cornwall, Alan was the son of Ellen (nee Berryman) and Alfred Eddy. His mother was a teacher; his father worked as an assayer (working out how much metal there was in rocks) in the local tin mines and later, after qualifying as ...
Source: Guardian Unlimited Science - November 29, 2017 Category: Science Authors: Dan Eddy Tags: Biochemistry and molecular biology Source Type: news
How a biophysical simulation method might accelerate drug target discovery
(American Society for Biochemistry and Molecular Biology) Researchers at the California Institute of Technology have developed an approach to overcome a major stumbling block in testing new drug targets. The research is reported in a Nov. 24 paper in the Journal of Biological Chemistry. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - November 29, 2017 Category: Biology Source Type: news
Biologists taught infusoria to fight poisons
(Lomonosov Moscow State University) A team of scientists from the Faculty of Biology of Lomonosov Moscow State University and Laboratory of Aerobic Metabolism in Microorganisms of Skryabin Institute of Biochemistry and Physiology of Microorganisms of the Russian Academy of Sciences found a new substance with anti-oxidant properties able protect living organisms from various toxic compounds. The results of the study were published in Preparative Biochemistry and Biotechnology magazine. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - November 29, 2017 Category: Biology Source Type: news
Structural insights into ion conduction by channelrhodopsin 2
We present high-resolution structures of ChR2 and the C128T mutant, which has a markedly increased open-state lifetime. The structure reveals two cavities on the intracellular side and two cavities on the extracellular side. They are connected by extended hydrogen-bonding networks involving water molecules and side-chain residues. Central is the retinal Schiff base that controls and synchronizes three gates that separate the cavities. Separate from this network is the DC gate that comprises a water-mediated bond between C128 and D156 and interacts directly with the retinal Schiff base. Comparison with the C128T structure r...
Source: ScienceNOW - November 23, 2017 Category: Science Authors: Volkov, O., Kovalev, K., Polovinkin, V., Borshchevskiy, V., Bamann, C., Astashkin, R., Marin, E., Popov, A., Balandin, T., Willbold, D., Büldt, G., Bamberg, E., Gordeliy, V. Tags: Biochemistry, Online Only r-articles Source Type: news
Webinar | CRISPR unleashed: New tools and applications in live-cell imaging
Source: ScienceNOW - November 23, 2017 Category: Science Authors: Grunwald, D., Yildiz, A., Barszczewski, M. Tags: Biochemistry, Cell Biology, Development, Medicine, Diseases, Molecular Biology opms-sups Source Type: news
Crystal structure of a TAPBPR-MHC I complex reveals the mechanism of peptide editing in antigen presentation
We report the crystal structure of MHC I in complex with the peptide editor TAPBPR (TAP-binding protein–related), a tapasin homolog. TAPBPR remodels the peptide-binding groove of MHC I, resulting in the release of low-affinity peptide. Changes include groove relaxation, modifications of key binding pockets, and domain adjustments. This structure captures a peptide-receptive state of MHC I and provides insights into the mechanism of peptide editing by TAPBPR and, by analogy, tapasin. (Source: ScienceNOW)
Source: ScienceNOW - November 23, 2017 Category: Science Authors: Jiang, J., Natarajan, K., Boyd, L. F., Morozov, G. I., Mage, M. G., Margulies, D. H. Tags: Biochemistry, Immunology reports Source Type: news
Structure of the TAPBPR-MHC I complex defines the mechanism of peptide loading and editing
Adaptive immunity is shaped by a selection of peptides presented on major histocompatibility complex class I (MHC I) molecules. The chaperones Tapasin (Tsn) and TAP-binding protein–related (TAPBPR) facilitate MHC I peptide loading and high-affinity epitope selection. Despite the pivotal role of Tsn and TAPBPR in controlling the hierarchical immune response, their catalytic mechanism remains unknown. Here, we present the x-ray structure of the TAPBPR–MHC I complex, which delineates the central step of catalysis. TAPBPR functions as peptide selector by remodeling the MHC I α2-1-helix region, stabilizing the...
Source: ScienceNOW - November 23, 2017 Category: Science Authors: Thomas, C., Tampe, R. Tags: Biochemistry, Immunology reports Source Type: news
Architecture of eukaryotic mRNA 3'-end processing machinery
Newly transcribed eukaryotic precursor messenger RNAs (pre-mRNAs) are processed at their 3' ends by the ~1-megadalton multiprotein cleavage and polyadenylation factor (CPF). CPF cleaves pre-mRNAs, adds a polyadenylate tail, and triggers transcription termination, but it is unclear how its various enzymes are coordinated and assembled. Here, we show that the nuclease, polymerase, and phosphatase activities of yeast CPF are organized into three modules. Using electron cryomicroscopy, we determined a 3.5-angstrom-resolution structure of the ~200-kilodalton polymerase module. This revealed four β propellers, in an assembl...
Source: ScienceNOW - November 23, 2017 Category: Science Authors: Casanal, A., Kumar, A., Hill, C. H., Easter, A. D., Emsley, P., Degliesposti, G., Gordiyenko, Y., Santhanam, B., Wolf, J., Wiederhold, K., Dornan, G. L., Skehel, M., Robinson, C. V., Passmore, L. A. Tags: Biochemistry, Molecular Biology reports Source Type: news
Matter: Young Again: How One Cell Turns Back Time
With every birth, cells begin anew. Scientists have found a biological mechanism underpinning the process in worms, which one day may be harnessed to restore our own damaged cells. (Source: NYT Health)
Source: NYT Health - November 22, 2017 Category: Consumer Health News Authors: CARL ZIMMER Tags: Worms Eggs Sperm Genetics and Heredity Biology and Biochemistry Calico (California Life Company) Source Type: news
Antibiotics resistance: Researchers succeed to block genes of resistance
(University of Montreal) Scientists at Universit é de Montreal's Department of Biochemistry and Molecular Medicine design better molecules that make it harder for plasmids to move between bacteria. (Source: EurekAlert! - Infectious and Emerging Diseases)
Source: EurekAlert! - Infectious and Emerging Diseases - November 22, 2017 Category: Infectious Diseases Source Type: news
Inner clock: Biologists research the mechanism of an auxiliary clock
(Bielefeld University) In December, the Nobel Prize for Medicine and Physiology will be awarded for the identification of genes that control the inner clock. The honored academics examined fruit flies to determine the biorhythm. Biochemist Professor Dr. Dorothee Staiger of Bielefeld University has been researching the inner clock of plants for 20 years. Her team has now published a new study in the research journal Genome Biology. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - November 17, 2017 Category: Biology Source Type: news
Structural basis of bacterial transcription activation
In bacteria, the activation of gene transcription at many promoters is simple and only involves a single activator. The cyclic adenosine 3',5'-monophosphate receptor protein (CAP), a classic activator, is able to activate transcription independently through two different mechanisms. Understanding the class I mechanism requires an intact transcription activation complex (TAC) structure at a high resolution. Here we report a high-resolution cryo–electron microscopy structure of an intact Escherichia coli class I TAC containing a CAP dimer, a 70–RNA polymerase (RNAP) holoenzyme, a complete class I CAP-dependent pr...
Source: ScienceNOW - November 16, 2017 Category: Science Authors: Liu, B., Hong, C., Huang, R. K., Yu, Z., Steitz, T. A. Tags: Biochemistry reports Source Type: news
Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass
Ammonia is a ubiquitous by-product of cellular metabolism; however, the biological consequences of ammonia production are not fully understood, especially in cancer. We found that ammonia is not merely a toxic waste product but is recycled into central amino acid metabolism to maximize nitrogen utilization. In our experiments, human breast cancer cells primarily assimilated ammonia through reductive amination catalyzed by glutamate dehydrogenase (GDH); secondary reactions enabled other amino acids, such as proline and aspartate, to directly acquire this nitrogen. Metabolic recycling of ammonia accelerated proliferation of ...
Source: ScienceNOW - November 16, 2017 Category: Science Authors: Spinelli, J. B., Yoon, H., Ringel, A. E., Jeanfavre, S., Clish, C. B., Haigis, M. C. Tags: Biochemistry, Medicine, Diseases reports Source Type: news
Atomic model for the dimeric FO region of mitochondrial ATP synthase
Mitochondrial adenosine triphosphate (ATP) synthase produces the majority of ATP in eukaryotic cells, and its dimerization is necessary to create the inner membrane folds, or cristae, characteristic of mitochondria. Proton translocation through the membrane-embedded FO region turns the rotor that drives ATP synthesis in the soluble F1 region. Although crystal structures of the F1 region have illustrated how this rotation leads to ATP synthesis, understanding how proton translocation produces the rotation has been impeded by the lack of an experimental atomic model for the FO region. Using cryo–electron microscopy, we...
Source: ScienceNOW - November 16, 2017 Category: Science Authors: Guo, H., Bueler, S. A., Rubinstein, J. L. Tags: Biochemistry reports Source Type: news
The structural basis of flagellin detection by NAIP5: A strategy to limit pathogen immune evasion
Robust innate immune detection of rapidly evolving pathogens is critical for host defense. Nucleotide-binding domain leucine-rich repeat (NLR) proteins function as cytosolic innate immune sensors in plants and animals. However, the structural basis for ligand-induced NLR activation has so far remained unknown. NAIP5 (NLR family, apoptosis inhibitory protein 5) binds the bacterial protein flagellin and assembles with NLRC4 to form a multiprotein complex called an inflammasome. Here we report the cryo–electron microscopy structure of the assembled ~1.4-megadalton flagellin-NAIP5-NLRC4 inflammasome, revealing how a liga...
Source: ScienceNOW - November 16, 2017 Category: Science Authors: Tenthorey, J. L., Haloupek, N., Lopez-Blanco, J. R., Grob, P., Adamson, E., Hartenian, E., Lind, N. A., Bourgeois, N. M., Chacon, P., Nogales, E., Vance, R. E. Tags: Biochemistry, Immunology r-articles Source Type: news
Developing new molecular methods for synthetizing treatments for drug-resistant cancers
(Worcester Polytechnic Institute) With a $1.7 million award from the National Institutes of Health (NIH), Anita Mattson, a biochemist at Worcester Polytechnic Institute (WPI), will develop a new class of catalysts that could make it possible to reliably synthesize organic compounds that hold the promise of treating cancers that have become resistant to commonly used chemotherapy medications. The catalysts may also open the door to a new approach to discovering new drugs for cancer and many other diseases. (Source: EurekAlert! - Cancer)
Source: EurekAlert! - Cancer - November 15, 2017 Category: Cancer & Oncology Source Type: news
Worcester Polytechnic Institute Biochemist Receives $1.7 Million NIH...
With the R35 award, designed to encourage investigators to embark on long-term projects of unusual potential, Anita Mattson will explore a new class of catalysts that could be useful tools for...(PRWeb November 15, 2017)Read the full story at http://www.prweb.com/releases/2017/11/prweb14922748.htm (Source: PRWeb: Medical Pharmaceuticals)
Source: PRWeb: Medical Pharmaceuticals - November 15, 2017 Category: Pharmaceuticals Source Type: news
Antibiotic Discovery in the Abyss
Combining the innovations of synthetic biology with robotic environmental sampling, a team of University of Bristol researchers are travelling to some of the most ‘ extreme ’ environments on Earth, including Atlantic depths of 4.5km, to find new leads which could help in the global fight against antimicrobial resistance. (Source: University of Bristol news)
Source: University of Bristol news - November 14, 2017 Category: Universities & Medical Training Tags: Grants and Awards, Health, International, Public engagement, Research, Postgraduate, Undergraduate; Faculty of Biomedical Sciences, Faculty of Biomedical Sciences, School of Biochemistry, Institutes, Bristol BioDesign Institute Source Type: news
Immune system intelligence: Your biochemistry "morphs" to defend against new parasites
(Natural News) Researchers discovered how the immune systems of certain species evolve to better adapt to new parasitic threats, all the while maintaining critical immune function that remained virtually unchanged for over millions of years, in a study published in the journal Nature Communications. Scientists from the University of East Anglia, U.K. and Dalhousie University, Canada... (Source: NaturalNews.com)
Source: NaturalNews.com - November 11, 2017 Category: Consumer Health News Source Type: news
Human cells and microorganisms found to be biochemically similar, according to astonishing study
(Natural News) Archaea are single-celled microorganisms that exist in areas with extreme conditions, such as volcanic vents in the ocean floor. A recent study has proven that these “hardy microbes” and human cells have similar biochemical compositions. Tom Santangelo, a Colorado State University (CSU) researcher and associate professor in the Department of Biochemistry and Molecular... (Source: NaturalNews.com)
Source: NaturalNews.com - November 11, 2017 Category: Consumer Health News Source Type: news
Medical News Today: Bugs in the basement? Here's why
A new study of arthropods in 50 U.S. homes suggests that their diversity is influenced more by access to the outdoors than the behavior of human residents. (Source: Health News from Medical News Today)
Source: Health News from Medical News Today - November 10, 2017 Category: Consumer Health News Tags: Biology / Biochemistry Source Type: news
Senior Research Laboratory Technician – full-time (Fixed Term)
Location Department of Physiology, Development and NeuroscienceSalary:£22,214 -£25,728Reference: PM13702Closing Date: 30 November 2017 We are looking for an experienced and enthusiastic individual to join the groups ofProfessor Abigail Fowden andDr Andrew Murray. Collectively, their research focuses on mitochondrial function during development and ageing, and how conditions during early life programme development and increase susceptibility to adult-onset degenerative diseases. They will provide mainly molecular biology support as well as some ass...
Source: Society for Endocrinology - November 10, 2017 Category: Endocrinology Source Type: news
Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes
The lysosome degrades and recycles macromolecules, signals to the cytosol and nucleus, and is implicated in many diseases. Here, we describe a method for the rapid isolation of mammalian lysosomes and use it to quantitatively profile lysosomal metabolites under various cell states. Under nutrient-replete conditions, many lysosomal amino acids are in rapid exchange with those in the cytosol. Loss of lysosomal acidification through inhibition of the vacuolar H+–adenosine triphosphatase (V-ATPase) increased the luminal concentrations of most metabolites but had no effect on those of the majority of essential amino acids...
Source: ScienceNOW - November 9, 2017 Category: Science Authors: Abu-Remaileh, M., Wyant, G. A., Kim, C., Laqtom, N. N., Abbasi, M., Chan, S. H., Freinkman, E., Sabatini, D. M. Tags: Biochemistry reports Source Type: news
SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway
mTOR complex 1 (mTORC1) regulates cell growth and metabolism in response to multiple environmental cues. Nutrients signal via the Rag guanosine triphosphatases (GTPases) to promote the localization of mTORC1 to the lysosomal surface, its site of activation. We identified SAMTOR, a previously uncharacterized protein, which inhibits mTORC1 signaling by interacting with GATOR1, the GTPase activating protein (GAP) for RagA/B. We found that the methyl donor S-adenosylmethionine (SAM) disrupts the SAMTOR-GATOR1 complex by binding directly to SAMTOR with a dissociation constant of approximately 7 μM. In cells, methionine starv...
Source: ScienceNOW - November 9, 2017 Category: Science Authors: Gu, X., Orozco, J. M., Saxton, R. A., Condon, K. J., Liu, G. Y., Krawczyk, P. A., Scaria, S. M., Harper, J. W., Gygi, S. P., Sabatini, D. M. Tags: Biochemistry, Cell Biology reports Source Type: news