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- Biological Transport (3)
- Mast cell (2)
- SNARE Proteins (2)
- 3’UTR (1)
- APOBEC3G (1)
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- Adaptive (1)
- Allergy (1)
- Allergy, exocytosis (1)
- Allosteric binding site (1)
- Amyotrophic lateral sclerosis (1)
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- DNA binding (1)
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- Documents for the photosynthesis project (1)
- Exocytosis (1)
- Experimental fitness (1)
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- Models, Biological (1)
- Molecular dynamics simulation (1)
- Neuraminidase inhibitor (1)
- Oseltamivir (1)
- P15NC (1)
- Peptides (1)
- Profilin 1 (1)
- Protease (1)
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Articles 1 - 28 of 28
Full-Text Articles in Life Sciences
Staufen Negatively Modulates Microrna Activity In Caenorhabditis Elegans, Zhiji Ren, Isana Veksler-Lublinsky, David Morrissey, Victor Ambros
Staufen Negatively Modulates Microrna Activity In Caenorhabditis Elegans, Zhiji Ren, Isana Veksler-Lublinsky, David Morrissey, Victor Ambros
Victor R. Ambros
The double-stranded RNA-binding protein Staufen has been implicated in various post-transcriptional gene regulatory processes. Here we demonstrate that the Caenorhabditis elegans homolog of Staufen, STAU-1, functionally interacts with microRNAs. Loss-of-function mutations of stau-1 significantly suppress phenotypes of let-7 family microRNA mutants, a hypomorphic allele of dicer and a lsy-6 microRNA partial loss-of-function mutant. Furthermore, STAU-1 modulates the activity of lin-14, a target of lin-4 and let-7 family microRNAs, and this modulation is abolished when the 3' untranslated region of lin-14 is removed. Deep sequencing of small RNA cDNA libraries reveals no dramatic change in the levels of microRNAs, or other …
The Ssdna Mutator Apobec3a Is Regulated By Cooperative Dimerization, Markus-Frederik Bohn, Shivender Shandilya, Tania Silvas, Ellen Nalivaika, Takahide Kouno, Brian Kelch, Sean Ryder, Nese Yilmaz, Mohan Somasundaran, Celia Schiffer
The Ssdna Mutator Apobec3a Is Regulated By Cooperative Dimerization, Markus-Frederik Bohn, Shivender Shandilya, Tania Silvas, Ellen Nalivaika, Takahide Kouno, Brian Kelch, Sean Ryder, Nese Yilmaz, Mohan Somasundaran, Celia Schiffer
Celia A. Schiffer
Deaminase activity mediated by the human APOBEC3 family of proteins contributes to genomic instability and cancer. APOBEC3A is by far the most active in this family and can cause rapid cell death when overexpressed, but in general how the activity of APOBEC3s is regulated on a molecular level is unclear. In this study, the biochemical and structural basis of APOBEC3A substrate binding and specificity is elucidated. We find that specific binding of single-stranded DNA is regulated by the cooperative dimerization of APOBEC3A. The crystal structure elucidates this homodimer as a symmetric domain swap of the N-terminal residues. This dimer interface …
Structure Of The Vif-Binding Domain Of The Antiviral Enzyme Apobec3g, Takahide Kouno, Elizabeth Luengas, Megumi Shigematsu, Shivender Shandilya, Jingying Zhang, Luan Chen, Mayuko Hara, Celia Schiffer, Reuben Harris, Hiroshi Matsuo
Structure Of The Vif-Binding Domain Of The Antiviral Enzyme Apobec3g, Takahide Kouno, Elizabeth Luengas, Megumi Shigematsu, Shivender Shandilya, Jingying Zhang, Luan Chen, Mayuko Hara, Celia Schiffer, Reuben Harris, Hiroshi Matsuo
Celia A. Schiffer
The human APOBEC3G (A3G) DNA cytosine deaminase restricts and hypermutates DNA-based parasites including HIV-1. The viral infectivity factor (Vif) prevents restriction by triggering A3G degradation. Although the structure of the A3G catalytic domain is known, the structure of the N-terminal Vif-binding domain has proven more elusive. Here, we used evolution- and structure-guided mutagenesis to solubilize the Vif-binding domain of A3G, thus permitting structural determination by NMR spectroscopy. A smaller zinc-coordinating pocket and altered helical packing distinguish the structure from previous catalytic-domain structures and help to explain the reported inactivity of this domain. This soluble A3G N-terminal domain is bound by …
Simultaneously Targeting The Ns3 Protease And Helicase Activities For More Effective Hepatitis C Virus Therapy, Jean Ndjomou, M Corby, Noreena Sweeney, Alicia Hanson, Cihan Aydin, Akbar Ali, Celia Schiffer, Kelin Li, Kevin Frankowski, Frank Schoenen, David Frick
Simultaneously Targeting The Ns3 Protease And Helicase Activities For More Effective Hepatitis C Virus Therapy, Jean Ndjomou, M Corby, Noreena Sweeney, Alicia Hanson, Cihan Aydin, Akbar Ali, Celia Schiffer, Kelin Li, Kevin Frankowski, Frank Schoenen, David Frick
Celia A. Schiffer
This study examines the specificity and mechanism of action of a recently reported hepatitis C virus (HCV) nonstructural protein 3 (NS3) helicase-protease inhibitor (HPI), and the interaction of HPI with the NS3 protease inhibitors telaprevir, boceprevir, danoprevir, and grazoprevir. HPI most effectively reduced cellular levels of subgenomic genotype 4a replicons, followed by genotypes 3a and 1b replicons. HPI had no effect on HCV genotype 2a or dengue virus replicon levels. Resistance evolved more slowly to HPI than telaprevir, and HPI inhibited telaprevir-resistant replicons. Molecular modeling and analysis of the ability of HPI to inhibit peptide hydrolysis catalyzed by a variety …
Structural Basis For Mutation-Induced Destabilization Of Profilin 1 In Als, Sivakumar Boopathy, Tania Silvas, Maeve Tischbein, Silvia Jansen, Shivender Shandilya, Jill Zitzewitz, John Landers, Bruce Goode, Celia Schiffer, Daryl Bosco
Structural Basis For Mutation-Induced Destabilization Of Profilin 1 In Als, Sivakumar Boopathy, Tania Silvas, Maeve Tischbein, Silvia Jansen, Shivender Shandilya, Jill Zitzewitz, John Landers, Bruce Goode, Celia Schiffer, Daryl Bosco
Celia A. Schiffer
Mutations in profilin 1 (PFN1) are associated with amyotrophic lateral sclerosis (ALS); however, the pathological mechanism of PFN1 in this fatal disease is unknown. We demonstrate that ALS-linked mutations severely destabilize the native conformation of PFN1 in vitro and cause accelerated turnover of the PFN1 protein in cells. This mutation-induced destabilization can account for the high propensity of ALS-linked variants to aggregate and also provides rationale for their reported loss-of-function phenotypes in cell-based assays. The source of this destabilization is illuminated by the X-ray crystal structures of several PFN1 proteins, revealing an expanded cavity near the protein core of the …
Inhibition Of Apobec3g Activity Impedes Double-Stranded Dna Repair, Ponnandy Prabhu, Shivender Shandilya, Elena Britan-Rosich, Adi Nagler, Celia Schiffer, Moshe Kotler
Inhibition Of Apobec3g Activity Impedes Double-Stranded Dna Repair, Ponnandy Prabhu, Shivender Shandilya, Elena Britan-Rosich, Adi Nagler, Celia Schiffer, Moshe Kotler
Celia A. Schiffer
The cellular cytidine deaminase APOBEC3G (A3G) was first described as an anti-HIV-1 restriction factor, acting by directly deaminating reverse transcripts of the viral genome. HIV-1 Vif neutralizes the activity of A3G, primarily by mediating degradation of A3G to establish effective infection in host target cells. Lymphoma cells, which express high amounts of A3G, can restrict Vif-deficient HIV-1. Interestingly, these cells are more stable in the face of treatments that result in double-stranded DNA damage, such as ionizing radiation and chemotherapies. Previously, we showed that the Vif-derived peptide (Vif25-39) efficiently inhibits A3G deamination, and increases the sensitivity of lymphoma cells to …
Rediii: A Pipeline For Automated Structure Solution, Markus-Frederik Bohn, Celia Schiffer
Rediii: A Pipeline For Automated Structure Solution, Markus-Frederik Bohn, Celia Schiffer
Celia A. Schiffer
High-throughput crystallographic approaches require integrated software solutions to minimize the need for manual effort. REdiii is a system that allows fully automated crystallographic structure solution by integrating existing crystallographic software into an adaptive and partly autonomous workflow engine. The program can be initiated after collecting the first frame of diffraction data and is able to perform processing, molecular-replacement phasing, chain tracing, ligand fitting and refinement without further user intervention. Preset values for each software component allow efficient progress with high-quality data and known parameters. The adaptive workflow engine can determine whether some parameters require modifications and choose alternative software strategies …
Modulation Of Hiv Protease Flexibility By The T80n Mutation, Hao Zhou, Shangyang Li, John Badger, Ellen Nalivaika, Yufeng Cai, Jennifer Foulkes-Murzycki, Celia Schiffer, Lee Makowski
Modulation Of Hiv Protease Flexibility By The T80n Mutation, Hao Zhou, Shangyang Li, John Badger, Ellen Nalivaika, Yufeng Cai, Jennifer Foulkes-Murzycki, Celia Schiffer, Lee Makowski
Celia A. Schiffer
The flexibility of HIV protease (HIVp) plays a critical role in enabling enzymatic activity and is required for substrate access to the active site. While the importance of flexibility in the flaps that cover the active site is well known, flexibility in other parts of the enzyme is also critical for function. One key region is a loop containing Thr 80, which forms the walls of the active site. Although not situated within the active site, amino acid Thr80 is absolutely conserved. The mutation T80N preserves the structure of the enzyme but catalytic activity is completely lost. To investigate the …
A Direct Interaction With Rna Dramatically Enhances The Catalytic Activity Of The Hiv-1 Protease In Vitro, Marc Potempa, Ellen Nalivaika, Debra Ragland, Sook-Kyung Lee, Celia Schiffer, Ronald Swanstrom
A Direct Interaction With Rna Dramatically Enhances The Catalytic Activity Of The Hiv-1 Protease In Vitro, Marc Potempa, Ellen Nalivaika, Debra Ragland, Sook-Kyung Lee, Celia Schiffer, Ronald Swanstrom
Celia A. Schiffer
Though the steps of human immunodeficiency virus type 1 (HIV-1) virion maturation are well documented, the mechanisms regulating the proteolysis of the Gag and Gag-Pro-Pol polyproteins by the HIV-1 protease (PR) remain obscure. One proposed mechanism argues that the maturation intermediate p15NC must interact with RNA for efficient cleavage by the PR. We investigated this phenomenon and found that processing of multiple substrates by the HIV-1 PR was enhanced in the presence of RNA. The acceleration of proteolysis occurred independently from the substrate's ability to interact with nucleic acid, indicating that a direct interaction between substrate and RNA is not …
A Balance Between Inhibitor Binding And Substrate Processing Confers Influenza Drug Resistance, Li Jiang, Ping Liu, Claudia Bank, Nicholas Renzette, Kristina Prachanronarong, L. Yilmaz, Daniel Caffrey, Konstantin Zeldovich, Celia Schiffer, Timothy Kowalik, Jeffrey Jensen, Robert Finberg, Jennifer Wang, Daniel Bolon
A Balance Between Inhibitor Binding And Substrate Processing Confers Influenza Drug Resistance, Li Jiang, Ping Liu, Claudia Bank, Nicholas Renzette, Kristina Prachanronarong, L. Yilmaz, Daniel Caffrey, Konstantin Zeldovich, Celia Schiffer, Timothy Kowalik, Jeffrey Jensen, Robert Finberg, Jennifer Wang, Daniel Bolon
Celia A. Schiffer
The therapeutic benefits of the neuraminidase (NA) inhibitor oseltamivir are dampened by the emergence of drug resistance mutations in influenza A virus (IAV). To investigate the mechanistic features that underlie resistance, we developed an approach to quantify the effects of all possible single-nucleotide substitutions introduced into important regions of NA. We determined the experimental fitness effects of 450 nucleotide mutations encoding positions both surrounding the active site and at more distant sites in an N1 strain of IAV in the presence and absence of oseltamivir. NA mutations previously known to confer oseltamivir resistance in N1 strains, including H275Y and N295S, …
Structural And Thermodynamic Effects Of Macrocyclization In Hcv Ns3/4a Inhibitor Mk-5172, Djade Soumana, Nese Yilmaz, Kristina Prachanronarong, Cihan Aydin, Akbar Ali, Celia Schiffer
Structural And Thermodynamic Effects Of Macrocyclization In Hcv Ns3/4a Inhibitor Mk-5172, Djade Soumana, Nese Yilmaz, Kristina Prachanronarong, Cihan Aydin, Akbar Ali, Celia Schiffer
Celia A. Schiffer
Recent advances in direct-acting antivirals against Hepatitis C Virus (HCV) have led to the development of potent inhibitors, including MK-5172, that target the viral NS3/4A protease with relatively low susceptibility to resistance. MK-5172 has a P2-P4 macrocycle and a unique binding mode among current protease inhibitors where the P2 quinoxaline packs against the catalytic residues H57 and D81. However, the effect of macrocyclization on this binding mode is not clear, as is the relation between macrocyclization, thermodynamic stabilization, and susceptibility to the resistance mutation A156T. We have determined high-resolution crystal structures of linear and P1-P3 macrocyclic analogs of MK-5172 bound …
Testing The Metabolic Theory Of Ecology., Andrew Kerkhoff
Testing The Metabolic Theory Of Ecology., Andrew Kerkhoff
Andrew J Kerkhoff
The metabolic theory of ecology (MTE) predicts the effects of body size and temperature on metabolism through considerations of vascular distribution networks and biochemical kinetics. MTE has also been extended to characterise processes from cellular to global levels. MTE has generated both enthusiasm and controversy across a broad range of research areas. However, most efforts that claim to validate or invalidate MTE have focused on testing predictions. We argue that critical evaluation of MTE also requires strong tests of both its theoretical foundations and simplifying assumptions. To this end, we synthesise available information and find that MTE's original derivations require …
List Of Thylakoid Zinc-Finger Proteins In Arabidopsis, Yan Lu
List Of Thylakoid Zinc-Finger Proteins In Arabidopsis, Yan Lu
Yan Lu
No abstract provided.
The Occurrence Of A Thylakoid-Localized Small Zinc Finger Protein In Land Plants, Yan Lu
The Occurrence Of A Thylakoid-Localized Small Zinc Finger Protein In Land Plants, Yan Lu
Yan Lu
No abstract provided.
A Small Zinc Finger Thylakoid Protein Plays A Role In Maintenance Of Photosystem Ii In Arabidopsis Thaliana, Yan Lu, David Hall, Robert Last
A Small Zinc Finger Thylakoid Protein Plays A Role In Maintenance Of Photosystem Ii In Arabidopsis Thaliana, Yan Lu, David Hall, Robert Last
Yan Lu
No abstract provided.
Chloroplast 2010: A Database For Large-Scale Phenotypic Screening Of Arabidopsis Mutants, Yan Lu, Linda Savage, Matthew Larson, Curtis Wilkerson, Robert Last
Chloroplast 2010: A Database For Large-Scale Phenotypic Screening Of Arabidopsis Mutants, Yan Lu, Linda Savage, Matthew Larson, Curtis Wilkerson, Robert Last
Yan Lu
No abstract provided.
Chloroplast Phenomics: Systematic Phenotypic Screening Of Chloroplast Protein Mutants In Arabidopsis, Yan Lu, Linda Savage, Robert Last
Chloroplast Phenomics: Systematic Phenotypic Screening Of Chloroplast Protein Mutants In Arabidopsis, Yan Lu, Linda Savage, Robert Last
Yan Lu
No abstract provided.
Large Scale Reverse Genetics In Arabidopsis: Case Studies From The Chloroplast 2010 Project, Imad Ajjawi, Yan Lu, Linda Savage, Shannon Bell, Robert Last
Large Scale Reverse Genetics In Arabidopsis: Case Studies From The Chloroplast 2010 Project, Imad Ajjawi, Yan Lu, Linda Savage, Shannon Bell, Robert Last
Yan Lu
No abstract provided.
Mechanism Of Cadmium-Mediated Inhibition Of Msh2-Msh6 Function In Dna Mismatch Repair, Manju Hingorani
Mechanism Of Cadmium-Mediated Inhibition Of Msh2-Msh6 Function In Dna Mismatch Repair, Manju Hingorani
Manju Hingorani
The observation that Cadmium (Cd(2+)) inhibits Msh2-Msh6, which is responsible for identifying base pair mismatches and other discrepancies in DNA, has led to the proposal that selective targeting of this protein and consequent suppression of DNA repair or apoptosis promote the carcinogenic effects of the heavy metal toxin. It has been suggested that Cd(2+) binding to specific sites on Msh2-Msh6 blocks its DNA binding and ATPase activities. To investigate the mechanism of inhibition, we measured Cd(2+) binding to Msh2-Msh6, directly and by monitoring changes in protein structure and enzymatic activity. Global fitting of the data to a multiligand binding model …
Web-Based Arabidopsis Functional And Structural Genomics Resources, Yan Lu, Robert Last
Web-Based Arabidopsis Functional And Structural Genomics Resources, Yan Lu, Robert Last
Yan Lu
No abstract provided.
New Connections Across Pathways And Cellular Processes: Industrialized Mutant Screening Reveals Novel Associations Between Diverse Phenotypes In Arabidopsis, Yan Lu, Linda Savage, Imad Ajjawi, Kathreen Imre, David Yoder, Christoph Benning, Dean Dellapenna, John Ohlrogge, Katherine Osteryoung, Andreas Weber, Curtis Wilkerson, Robert Last
New Connections Across Pathways And Cellular Processes: Industrialized Mutant Screening Reveals Novel Associations Between Diverse Phenotypes In Arabidopsis, Yan Lu, Linda Savage, Imad Ajjawi, Kathreen Imre, David Yoder, Christoph Benning, Dean Dellapenna, John Ohlrogge, Katherine Osteryoung, Andreas Weber, Curtis Wilkerson, Robert Last
Yan Lu
No abstract provided.
The Importance Of Maltose In Transitory Starch Breakdown, Yan Lu, Thomas Sharkey
The Importance Of Maltose In Transitory Starch Breakdown, Yan Lu, Thomas Sharkey
Yan Lu
No abstract provided.
Cellular And Organ Level Localization Of Maltose In Maltose-Excess Arabidopsis Mutants, Yan Lu, Jon Steichen, Sean Weise, Thomas Sharkey
Cellular And Organ Level Localization Of Maltose In Maltose-Excess Arabidopsis Mutants, Yan Lu, Jon Steichen, Sean Weise, Thomas Sharkey
Yan Lu
No abstract provided.
The Role Of Cytosolic A-Glucan Phosphorylase In Maltose Metabolism And The Comparison Of Amylomaltose In Arabidopsis And E. Coli, Yan Lu, Jon Steichen, Jian Yao, Thomas Sharkey
The Role Of Cytosolic A-Glucan Phosphorylase In Maltose Metabolism And The Comparison Of Amylomaltose In Arabidopsis And E. Coli, Yan Lu, Jon Steichen, Jian Yao, Thomas Sharkey
Yan Lu
No abstract provided.
The Role Of Amylomaltase In Maltose Metabolism In The Cytosol Of Photosynthetic Cells, Yan Lu, Thomas Sharkey
The Role Of Amylomaltase In Maltose Metabolism In The Cytosol Of Photosynthetic Cells, Yan Lu, Thomas Sharkey
Yan Lu
No abstract provided.
Compartmental Specificity Of Cellular Membrane Fusion Encoded In Snare Proteins, James Mcnew, Frank Parlati, Ryorichi Fukuda, Robert Johnston, Keren Paz, Fabienne Paumet, Thomas Sollner, James Rothman
Compartmental Specificity Of Cellular Membrane Fusion Encoded In Snare Proteins, James Mcnew, Frank Parlati, Ryorichi Fukuda, Robert Johnston, Keren Paz, Fabienne Paumet, Thomas Sollner, James Rothman
Fabienne Paumet
No abstract provided.
Soluble Nsf Attachment Protein Receptors (Snares) In Rbl-2h3 Mast Cells: Functional Role Of Syntaxin4 In Exocytosis And Identification Of A Vamp8-Containing Secretory Compartment, Fabienne Paumet, Joelle Le Mao, Sophie Martin, Thierry Galli, Bernard David, Ulrich Blank, Michele Roa
Soluble Nsf Attachment Protein Receptors (Snares) In Rbl-2h3 Mast Cells: Functional Role Of Syntaxin4 In Exocytosis And Identification Of A Vamp8-Containing Secretory Compartment, Fabienne Paumet, Joelle Le Mao, Sophie Martin, Thierry Galli, Bernard David, Ulrich Blank, Michele Roa
Fabienne Paumet
No abstract provided.
Involvement Of The Ras-Like Gtpase Rab3d In Rbl-2h3 Mast Cell Exocytosis Following Stimulation Via High Affinity Ige Receptors (Fcεri), Michele Roa, Fabienne Paumet, Joelle Le Mao, Bernard David, Ulrich Blank
Involvement Of The Ras-Like Gtpase Rab3d In Rbl-2h3 Mast Cell Exocytosis Following Stimulation Via High Affinity Ige Receptors (Fcεri), Michele Roa, Fabienne Paumet, Joelle Le Mao, Bernard David, Ulrich Blank
Fabienne Paumet
No abstract provided.