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Articles 121 - 150 of 205
Full-Text Articles in Amino Acids, Peptides, and Proteins
Mapping The Human Vasculature By In Vivo Phage Display, Julianna Bronk
Mapping The Human Vasculature By In Vivo Phage Display, Julianna Bronk
Dissertations and Theses (Open Access)
In vivo phage display screenings by intravenous injection of a random phage-displayed peptide library allow for the selection of peptides that localize to specific vascular beds. At the University of Texas MD Anderson Cancer Center, we have had the opportunity to perform phage display screenings in cancer patients in order to select for cancer specific targets directly in humans. These targets serve to define biochemical diversity of endothelial cell surfaces and can be validated and explored towards the design of vascular-targeted pharmacology. In the most recent patient screen, samples were recovered from hepatocellular carcinoma (HCC) as well as 26 additional …
Trnas As Regulators Of Biological Processes, Medha Raina, Michael Ibba
Trnas As Regulators Of Biological Processes, Medha Raina, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Transfer RNAs (tRNA) are best known for their role as adaptors during translation of the genetic code. Beyond their canonical role during protein biosynthesis, tRNAs also perform additional functions in both prokaryotes and eukaryotes for example in regulating gene expression. Aminoacylated tRNAs have also been implicated as substrates for non-ribosomal peptide bond formation, post-translational protein labeling, modification of phospholipids in the cell membrane, and antibiotic biosyntheses. Most recently tRNA fragments, or tRFs, have also been recognized to play regulatory roles. Here, we examine in more detail some of the new functions emerging for tRNA in a variety of cellular processes …
Oxidation Of Cellular Amino Acid Pools Leads To Cytotoxic Mistranslation Of The Genetic Code, Tammy J. Bullwinkle, Noah M. Reynolds, Medha Raina, Adil Moghal, Eleftheria Matsa, Andrei Rajkovic, Huseyin Kayadibi, Farbod Fazlollahi, Christopher Ryan, Nathaniel Howitz, Kym F. Faull, Beth A. Lazazzera, Michael Ibba
Oxidation Of Cellular Amino Acid Pools Leads To Cytotoxic Mistranslation Of The Genetic Code, Tammy J. Bullwinkle, Noah M. Reynolds, Medha Raina, Adil Moghal, Eleftheria Matsa, Andrei Rajkovic, Huseyin Kayadibi, Farbod Fazlollahi, Christopher Ryan, Nathaniel Howitz, Kym F. Faull, Beth A. Lazazzera, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Aminoacyl-tRNA synthetases use a variety of mechanisms to ensure fidelity of the genetic code and ultimately select the correct amino acids to be used in protein synthesis. The physiological necessity of these quality control mechanisms in different environments remains unclear, as the cost vs benefit of accurate protein synthesis is difficult to predict. We show that in Escherichia coli, a non-coded amino acid produced through oxidative damage is a significant threat to the accuracy of protein synthesis and must be cleared by phenylalanine-tRNA synthetase in order to prevent cellular toxicity caused by mis-synthesized proteins. These findings demonstrate how stress …
Reduced Amino Acid Specificity Of Mammalian Tyrosyl-Trna Synthetase Is Associated With Elevated Mistranslation Of Tyr Codons, Medha Raina, Adil Moghal, Amanda Kano, Mathew Jerums, Paul D. Schnier, Shun Luo, Rohini Deshpande, Pavel D. Bondarenko, Henry Lin, Michael Ibba
Reduced Amino Acid Specificity Of Mammalian Tyrosyl-Trna Synthetase Is Associated With Elevated Mistranslation Of Tyr Codons, Medha Raina, Adil Moghal, Amanda Kano, Mathew Jerums, Paul D. Schnier, Shun Luo, Rohini Deshpande, Pavel D. Bondarenko, Henry Lin, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Quality control operates at different steps in translation to limit errors to approximately one mistranslated codon per 10,000 codons during mRNA-directed protein synthesis. Recent studies have suggested that error rates may actually vary considerably during translation under different growth conditions. Here we examined the misincorporation of Phe at Tyr codons during synthesis of a recombinant antibody produced in tyrosine-limited Chinese hamster ovary (CHO) cells. Tyr to Phe replacements were previously found to occur throughout the antibody at a rate of up to 0.7% irrespective of the identity or context of the Tyr codon translated. Despite this comparatively high mistranslation rate, …
Molecular Chaperone Tools For Use Against Neurodegenerative Diseases, Matthew Tinkham
Molecular Chaperone Tools For Use Against Neurodegenerative Diseases, Matthew Tinkham
Senior Honors Projects
A noted characteristic found in several neurodegenerative disorders, including Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease and bovine spongiform encephalopathy, is the accumulation of amyloid plaques in the brain. Amyloid plaques contain deposits of fibrillar aggregates of misfolded proteins that disrupt normal functionality in neurons. Certain variants of these misfolded proteins are self-replicating; these self-replicating amyloids are termed prions (for infectious protein). We are interested in how protein misfolding contributes to amyloid formation and how molecular chaperone proteins can change the formation of amyloid deposits. Chaperone proteins function by catalyzing the proper folding of other proteins, the refolding of misfolded proteins, …
The Abcs Of The Ribosome, Kurt Fredrick, Michael Ibba
The Abcs Of The Ribosome, Kurt Fredrick, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
An ABC protein that binds the ribosomal exit site suggests a new mechanism for direct regulation of translation in response to changing ATP levels in the cell.
Molecular Evolution Of Protein-Rna Mimicry As A Mechanism For Translational Control, Assaf Katz, Lindsey Solden, S. Betty Zou, William Wiley Navarre, Michael Ibba
Molecular Evolution Of Protein-Rna Mimicry As A Mechanism For Translational Control, Assaf Katz, Lindsey Solden, S. Betty Zou, William Wiley Navarre, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Elongation factor P (EF-P) is a conserved ribosome-binding protein that structurally mimics tRNA to enable the synthesis of peptides containing motifs that otherwise would induce translational stalling, including polyproline. In many bacteria, EF-P function requires post-translational modification with (R)-β-lysine by the lysyl-tRNA synthetase paralog PoxA. To investigate how recognition of EF-P by PoxA evolved from tRNA recognition by aminoacyl-tRNA synthetases, we compared the roles of EF-P/PoxA polar contacts with analogous interactions in a closely related tRNA/synthetase complex. PoxA was found to recognize EF-P solely via identity elements in the acceptor loop, the domain of the protein that interacts with the …
Biochemical Assay Optimization And Computational Screening Efforts To Identify Potential Luxs Inhibitors, Keeshia Q. Wang
Biochemical Assay Optimization And Computational Screening Efforts To Identify Potential Luxs Inhibitors, Keeshia Q. Wang
Master's Theses
Quorum sensing (QS) is a process of coordination of bacterial gene expression in response to cell population. System two QS is regulated by the small signaling molecule autoinducer-2 (AI-2) and is implicated in the infectious behaviors of various bacterial species. AI-2 is biosynthesized from S-ribosylhomocysteine (SRH) by the enzyme LuxS and induces interspecies cell-to-cell communication. Inhibition of LuxS would therefore inhibit interspecies QS. Herein, a search for novel molecular species that will competitively bind with SRH in the LuxS binding site is performed in silico. Computational screening results are then validated in vitro using an optimized LuxS inhibition …
Killerflip: A Novel Lytic Peptide Specifically Inducing Cancer Cell Death, B Pennarun, G. Gaidos, O Bucur, A Tinari
Killerflip: A Novel Lytic Peptide Specifically Inducing Cancer Cell Death, B Pennarun, G. Gaidos, O Bucur, A Tinari
Dartmouth Scholarship
One of the objectives in the development of effective cancer therapy is induction of tumor-selective cell death. Toward this end, we have identified a small peptide that, when introduced into cells via a TAT cell-delivery system, shows a remarkably potent cytoxicity in a variety of cancer cell lines and inhibits tumor growth in vivo, whereas sparing normal cells and tissues. This fusion peptide was named killer FLIP as its sequence was derived from the C-terminal domain of c-FLIP, an anti-apoptotic protein. Using structure activity analysis, we determined the minimal bioactive core of killerFLIP, namely killerFLIP-E. Structural analysis of cells using …
Direction Of Aminoacylated Transfer Rnas Into Antibiotic Synthesis And Peptidoglycan-Mediated Antibiotic Resistance, Jennifer Shepherd, Michael Ibba
Direction Of Aminoacylated Transfer Rnas Into Antibiotic Synthesis And Peptidoglycan-Mediated Antibiotic Resistance, Jennifer Shepherd, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Prokaryotic aminoacylated‐transfer RNAs often need to be efficiently segregated between translation and other cellular biosynthetic pathways. Many clinically relevant bacteria, including Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa direct some aminoacylated‐tRNA species into peptidoglycan biosynthesis and/or membrane phospholipid modification. Subsequent indirect peptidoglycan cross‐linkage or change in membrane permeability is often a prerequisite for high‐level antibiotic resistance. In Streptomycetes, aminoacylated‐tRNA species are used for antibiotic synthesis as well as antibiotic resistance. The direction of coding aminoacylated‐tRNA molecules away from translation and into antibiotic resistance and synthesis pathways are discussed in this review.
Lipid Ii-Independent Trans Editing Of Mischarged Trnas By The Penicillin Resistance Factor Murm, Jennifer Shepherd, Michael Ibba
Lipid Ii-Independent Trans Editing Of Mischarged Trnas By The Penicillin Resistance Factor Murm, Jennifer Shepherd, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Streptococcus pneumoniae is a causative agent of nosocomial infections such as pneumonia, meningitis, and septicemia. Penicillin resistance in S. pneumoniae depends in part upon MurM, an aminoacyl-tRNA ligase that attaches l-serine or l-alanine to the stem peptide lysine of Lipid II in cell wall peptidoglycan. To investigate the exact substrates the translation machinery provides MurM, quality control by alanyl-tRNA synthetase (AlaRS) was investigated. AlaRS mischarged serine and glycine to tRNAAla, as observed in other bacteria, and also transferred alanine, serine, and glycine to tRNAPhe. S. pneumoniae tRNAPhe has an unusual U4:C69 mismatch in its acceptor stem that …
Divergent Protein Motifs Direct Ef-P Mediated Translational Regulation In Salmonella And Escherichia Coli, Steven J. Hersch, Mengchi Wang, S. Betty Zou, Kyung-Mee Moon, Leonard J. Foster, Michael Ibba, William Wiley Navarre
Divergent Protein Motifs Direct Ef-P Mediated Translational Regulation In Salmonella And Escherichia Coli, Steven J. Hersch, Mengchi Wang, S. Betty Zou, Kyung-Mee Moon, Leonard J. Foster, Michael Ibba, William Wiley Navarre
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Elongation factor P (EF-P) is a universally conserved bacterial translation factor homologous to eukaryotic/archaeal initiation factor 5A. In Salmonella, deletion of the efp gene results in pleiotropic phenotypes, including increased susceptibility to numerous cellular stressors. Only a limited number of proteins are affected by the loss of EF-P, and it has recently been determined that EF-P plays a critical role in rescuing ribosomes stalled at PPP and PPG peptide sequences. Here we present an unbiased in vivo investigation of the specific targets of EF-P by employing stable isotope labeling of amino acids in cell culture (SILAC) to compare the …
Revisiting The Fundamentals In The Design And Control Of Nanoparticulate Colloids In The Frame Of Soft Chemistry, Vuk Uskoković
Revisiting The Fundamentals In The Design And Control Of Nanoparticulate Colloids In The Frame Of Soft Chemistry, Vuk Uskoković
Pharmacy Faculty Articles and Research
This review presents thoughts on some of the fundamental features of conceptual models applied in the design of fine particles in the frames of colloid and soft chemistry. A special emphasis is placed on the limitations of these models, an acknowledgment of which is vital in improving their intricacy and effectiveness in predicting the outcomes of the corresponding experimental settings. Thermodynamics of self-assembly phenomena illustrated on the examples of protein assembly and micellization is analyzed in relation to the previously elaborated thesis that each self-assembly in reality presents a co-assembly, since it implies a mutual reorganization of the assembling system …
Synthesis And Biochemical Activities Of Antiproliferative Amino Acid And Phosphate Derivatives Of Microtubule-Disrupting Beta-Lactam Combretastatins, Niamh M. O'Boyle, Lisa M. Greene, Niall O. Keely, Shu Wang, Tadhg S. Cotter, Daniela M. Zisterer, Mary J. Meegan
Synthesis And Biochemical Activities Of Antiproliferative Amino Acid And Phosphate Derivatives Of Microtubule-Disrupting Beta-Lactam Combretastatins, Niamh M. O'Boyle, Lisa M. Greene, Niall O. Keely, Shu Wang, Tadhg S. Cotter, Daniela M. Zisterer, Mary J. Meegan
Articles
The synthesis and biochemical activities of novel water-soluble β-lactam analogues of combretastatin A-4 are described. The first series of compounds investigated, β-lactam phosphate esters 7a, 8a and 9a, exhibited potent antiproliferative activity and caused microtubule disruption in human breast carcinoma-derived MCF-7 cells. They did not inhibit tubulin polymerisation in vitro, indicating that biotransformation was necessary for their antiproliferative and tubulin binding effects in MCF-7 cells. The second series of compounds, β-lactam amino acid amides (including 10k and 11l) displayed potent antiproliferative activity in MCF-7 cells, disrupted microtubules in MCF-7 cells and also inhibited the polymerisation of …
(R)-Β-Lysine Modified Elongation Factor P Functions In Translation Elongation, Tammy J. Bullwinkle, S. Betty Zou, Andrei Rajkovic, Steven J. Hersch, Sara Elgamal, Nathaniel Robinson, David Smil, Yuri Bolshan, William Wiley Navarre, Michael Ibba
(R)-Β-Lysine Modified Elongation Factor P Functions In Translation Elongation, Tammy J. Bullwinkle, S. Betty Zou, Andrei Rajkovic, Steven J. Hersch, Sara Elgamal, Nathaniel Robinson, David Smil, Yuri Bolshan, William Wiley Navarre, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Post-translational modification of bacterial elongation factor P (EF-P) with (R)-β-lysine at a conserved lysine residue activates the protein in vivo and increases puromycin reactivity of the ribosome in vitro. The additional hydroxylation of EF-P at the same lysine residue by the YfcM protein has also recently been described. The roles of modified and unmodified EF-P during different steps in translation, and how this correlates to its physiological role in the cell, have recently been linked to the synthesis of polyproline stretches in proteins. Polysome analysis indicated that EF-P functions in translation elongation, rather than initiation as proposed previously. This was …
Selection Of Trna Charging Quality Control Mechanisms That Increase Mistranslation Of The Genetic Code, Srujana S. Yadavalli, Michael Ibba
Selection Of Trna Charging Quality Control Mechanisms That Increase Mistranslation Of The Genetic Code, Srujana S. Yadavalli, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Mistranslation can follow two events during protein synthesis: production of non-cognate amino acid:transfer RNA (tRNA) pairs by aminoacyl-tRNA synthetases (aaRSs) and inaccurate selection of aminoacyl-tRNAs by the ribosome. Many aaRSs actively edit non-cognate amino acids, but editing mechanisms are not evolutionarily conserved, and their physiological significance remains unclear. To address the connection between aaRSs and mistranslation, the evolutionary divergence of tyrosine editing by phenylalanyl-tRNA synthetase (PheRS) was used as a model. Certain PheRSs are naturally error prone, most notably a Mycoplasma example that displayed a low level of specificity consistent with elevated mistranslation of the proteome. Mycoplasma PheRS was found …
Taking Aim At The Start Of Translation, Medha Raina, Michael Ibba
Taking Aim At The Start Of Translation, Medha Raina, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
No abstract provided.
A Pseudo-Trna Modulates Antibiotic Resistance In Bacillus Cereus, Theresa E. Rogers, Sandro F. Ataide, Kiley Dare, Assaf Katz, Stephanie Seveau, Hervé Roy, Michael Ibba
A Pseudo-Trna Modulates Antibiotic Resistance In Bacillus Cereus, Theresa E. Rogers, Sandro F. Ataide, Kiley Dare, Assaf Katz, Stephanie Seveau, Hervé Roy, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Bacterial genomic islands are often flanked by tRNA genes, which act as sites for the integration of foreign DNA into the host chromosome. For example, Bacillus cereus ATCC14579 contains a pathogenicity island flanked by a predicted pseudo-tRNA, tRNAOther, which does not function in translation. Deletion of tRNAOther led to significant changes in cell wall morphology and antibiotic resistance and was accompanied by changes in the expression of numerous genes involved in oxidative stress responses, several of which contain significant complementarities to sequences surrounding tRNAOther. This suggested that tRNAOther might be expressed as part of a larger RNA, and RACE analysis …
Identification Of Persistent Long Range Interactions In GA95 And GB95 Through Thermal Unfolding Simulations, Milen Redai Tesfamariam
Identification Of Persistent Long Range Interactions In GA95 And GB95 Through Thermal Unfolding Simulations, Milen Redai Tesfamariam
Chemistry & Biochemistry Theses & Dissertations
For over five decades, different experiments have been performed to research how proteins attain their native three dimensional structures. However, the folding problem continues to be a puzzle in modern science. The design of two proteins that have maximal sequence identity but different folds and functions is one method that is being used to study the relationship between protein structure and amino acid sequence. In particular, mutant proteins of Streptococcus protein G, GA and GB, have 95% sequence identity and a 3a helix fold and β4/a fold, respectively. Molecular dynamics simulations of GA95 …
Association Of A Multi-Synthetase Complex With Translating Ribosomes In The Archaeon Thermococcus Kodakarensis, Medha Raina, Sara Elgamal, Thomas J. Santangelo, Michael Ibba
Association Of A Multi-Synthetase Complex With Translating Ribosomes In The Archaeon Thermococcus Kodakarensis, Medha Raina, Sara Elgamal, Thomas J. Santangelo, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
In archaea and eukaryotes aminoacyl-tRNA synthetases (aaRSs) associate in multi-synthetase complexes (MSCs), however the role of such MSCs in translation is unknown. MSC function was investigated in vivo in the archaeon Thermococcus kodakarensis, wherein six aaRSs were affinity co-purified together with several other factors involved in protein synthesis, suggesting that MSCs may interact directly with translating ribosomes. In support of this hypothesis, the aminoacyltRNA synthetase (aaRS) activities of the MSC were enriched in isolated T. kodakarensis polysome fractions. These data indicate that components of the archaeal protein synthesis machinery associate into macromolecular assemblies in vivo and provide the potential …
Cryo-Em Structure Of The Archaeal 50s Ribosomal Subunit In Complex With Initiation Factor 6 And Implications For Ribosome Evolution, Basil J. Greber, Daniel Boehringer, Vlatka Godinic-Mikulcic, Ana Crnkovic, Michael Ibba, Ivana Weygand-Durasevic, Nenad Ban
Cryo-Em Structure Of The Archaeal 50s Ribosomal Subunit In Complex With Initiation Factor 6 And Implications For Ribosome Evolution, Basil J. Greber, Daniel Boehringer, Vlatka Godinic-Mikulcic, Ana Crnkovic, Michael Ibba, Ivana Weygand-Durasevic, Nenad Ban
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Translation of mRNA into proteins by the ribosome is universally conserved in all cellular life. The composition and complexity of the translation machinery differ markedly between the three domains of life. Organisms from the domain Archaea show an intermediate level of complexity, sharing several additional components of the translation machinery with eukaryotes that are absent in bacteria. One of these translation factors is initiation factor 6 (IF6), which associates with the large ribosomal subunit. We have reconstructed the 50S ribosomal subunit from the archaeon Methanothermobacter thermautotrophicus in complex with archaeal IF6 at 6.6 Å resolution using cryo-electron microscopy (EM). The …
Roles Of Trna In Cell Wall Biosynthesis, Kiley Dare, Michael Ibba
Roles Of Trna In Cell Wall Biosynthesis, Kiley Dare, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Recent research into various aspects of bacterial metabolism such as cell wall and antibiotic synthesis, degradation pathways, cellular stress, and amino acid biosynthesis has elucidated roles of aminoacyl‐transfer ribonucleic acid (aa‐tRNA) outside of translation. Although the two enzyme families responsible for cell wall modifications, aminoacyl‐phosphatidylglycerol synthases (aaPGSs) and Fem, were discovered some time ago, they have recently become of intense interest for their roles in the antimicrobial resistance of pathogenic microorganisms. The addition of positively charged amino acids to phosphatidylglycerol (PG) by aaPGSs neutralizes the lipid bilayer making the bacteria less susceptible to positively charged antimicrobial agents. Fem transferases utilize …
Protein Structure Networks, Lesley H. Greene
Protein Structure Networks, Lesley H. Greene
Chemistry & Biochemistry Faculty Publications
The application of the field of network science to the scientific disciplines of structural biology and biochemistry, have yielded important new insights into the nature and determinants of protein structures, function, dynamics and the folding process. Advancements in further understanding protein relationships through network science have also reshaped the way we view the connectivity of proteins in the protein universe. The canonical hierarchical classification can now be visualized for example, as a protein fold continuum. This review will survey several key advances in the expanding area of research being conducted to study protein structures and folding using network approaches.
Beta-Lysine Discrimination By Lysyl-Trna Synthetase, Marla S. Gilreath, Hervé Roy, Tammy J. Bullwinkle, Assaf Katz, Michael Ibba, William Wiley Navarre
Beta-Lysine Discrimination By Lysyl-Trna Synthetase, Marla S. Gilreath, Hervé Roy, Tammy J. Bullwinkle, Assaf Katz, Michael Ibba, William Wiley Navarre
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Elongation factor P is modified with (R)‐β‐lysine by the lysyl‐tRNA synthetase (LysRS) paralog PoxA. PoxA specificity is orthogonal to LysRS, despite their high similarity. To investigate α‐ and β‐lysine recognition by LysRS and PoxA, amino acid replacements were made in the LysRS active site guided by the PoxA structure. A233S LysRS behaved as wild type with α‐lysine, while the G469A and A233S/G469A variants decreased stable α‐lysyl‐adenylate formation. A233S LysRS recognized β‐lysine better than wildtype, suggesting a role for this residue in discriminating α‐ and β‐amino acids. Both enantiomers of β‐lysine were substrates for tRNA aminoacylation by LysRS, which, together with …
The Trna Synthetase Paralog Poxa Modifies Elongation Factor-P With (R)-Β-Lysine, Hervé Roy, S. Betty Zou, Tammy J. Bullwinkle, Benjamin S. Wolfe, Marla S. Gilreath, Craig J. Forsyth, William Wiley Navarre, Michael Ibba
The Trna Synthetase Paralog Poxa Modifies Elongation Factor-P With (R)-Β-Lysine, Hervé Roy, S. Betty Zou, Tammy J. Bullwinkle, Benjamin S. Wolfe, Marla S. Gilreath, Craig J. Forsyth, William Wiley Navarre, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
The lysyl-tRNA synthetase paralog PoxA modifies elongation factor P (EF-P) with α-lysine at low efficiency. Cell-free extracts containing non–α-lysine substrates of PoxA modified EF-P with a change in mass consistent with addition of β-lysine, a substrate also predicted by genomic analyses. EF-P was efficiently functionally modified with (R)-β-lysine but not (S)-β-lysine or genetically encoded α-amino acids, indicating that PoxA has evolved an activity orthogonal to that of the canonical aminoacyl-tRNA synthetases.
Cloning, Expression, And Characterization Of The Aminoethylphosphonate Pathway In Trypanosoma Cruzi, Samuel I. Rodriguez^, Esteban M. Cordero, Igor C. Almeida*
Cloning, Expression, And Characterization Of The Aminoethylphosphonate Pathway In Trypanosoma Cruzi, Samuel I. Rodriguez^, Esteban M. Cordero, Igor C. Almeida*
COURI Symposium Abstracts, Summer 2011
No abstract provided.
An Archaeal Trna-Synthetase Complex That Enhances Aminoacylation Under Extreme Conditions, Vlatka Godinic-Mikulcic, Jelena Jaric, Corinne D. Hausmann, Michael Ibba, Ivana Weygand-Durasevic
An Archaeal Trna-Synthetase Complex That Enhances Aminoacylation Under Extreme Conditions, Vlatka Godinic-Mikulcic, Jelena Jaric, Corinne D. Hausmann, Michael Ibba, Ivana Weygand-Durasevic
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Aminoacyl-tRNA synthetases (aaRSs) play an integral role in protein synthesis, functioning to attach the correct amino acid with its cognate tRNA molecule. AaRSs are known to associate into higher-order multi-aminoacyl-tRNA synthetase complexes (MSC) involved in archaeal and eukaryotic translation, although the precise biological role remains largely unknown. To gain further insights into archaeal MSCs, possible protein-protein interactions with the atypical Methanothermobacter thermautotrophicus seryl-tRNA synthetase (MtSerRS) were investigated. Yeast two-hybrid analysis revealed arginyl-tRNA synthetase (MtArgRS) as an interacting partner of MtSerRS. Surface plasmon resonance confirmed stable complex formation, with a dissociation constant (KD) of 250 nm. Formation of the MtSerRS·MtArgRS complex …
Poxa, Yjek And Elongation Factor P Coordinately Modulate Virulence And Drug Resistance In Salmonella Enterica, William Wiley Navarre, Shicong Zou, Hervé Roy, Jinglin Lucy Xie, Alexei Savchenko, Alexander Singer, Elena Edvokimova, Lynne R. Prost, Runjun Kumar, Michael Ibba, Ferric C. Fang
Poxa, Yjek And Elongation Factor P Coordinately Modulate Virulence And Drug Resistance In Salmonella Enterica, William Wiley Navarre, Shicong Zou, Hervé Roy, Jinglin Lucy Xie, Alexei Savchenko, Alexander Singer, Elena Edvokimova, Lynne R. Prost, Runjun Kumar, Michael Ibba, Ferric C. Fang
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
We report an interaction between poxA, encoding a paralog of lysyl tRNA-synthetase, and the closely linked yjeK gene, encoding a putative 2,3-β-lysine aminomutase, that is critical for virulence and stress resistance in Salmonella enterica. Salmonella poxA and yjeK mutants share extensive phenotypic pleiotropy, including attenuated virulence in mice, an increased ability to respire under nutrient-limiting conditions, hypersusceptibility to a variety of diverse growth inhibitors, and altered expression of multiple proteins, including several encoded on the SPI-1 pathogenicity island. PoxA mediates posttranslational modification of bacterial elongation factor P (EF-P), analogous to the modification of the eukaryotic EF-P homolog, eIF5A, with …
Redox Status Affects The Catalytic Activity Of Glutamyl-Trna Synthetase, Assaf Katz, Ranat Banerjee, Merly De Armas, Michael Ibba, Omar Orellana
Redox Status Affects The Catalytic Activity Of Glutamyl-Trna Synthetase, Assaf Katz, Ranat Banerjee, Merly De Armas, Michael Ibba, Omar Orellana
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Glutamyl-tRNA synthetases (GluRS) provide Glu-tRNA for different processes including protein synthesis, glutamine transamidation and tetrapyrrole biosynthesis. Many organisms contain multiple GluRSs, but whether these duplications solely broaden tRNA specificity or also play additional roles in tetrapyrrole biosynthesis is not known. Previous studies have shown that GluRS1, one of two GluRSs from the extremophile Acidithiobacillus ferrooxidans, is inactivated when intracellular heme is elevated suggesting a specific role for GluRS1 in the regulation of tetrapyrrole biosynthesis. We now show that, in vitro, GluRS1 activity is reversibly inactivated upon oxidation by hemin and hydrogen peroxide. The targets for oxidation-based inhibition were …
Ricin B Chain-Insulin Fusion Protein Immunomodulation Of Type 1 Diabetes, James Edward Carter Iii
Ricin B Chain-Insulin Fusion Protein Immunomodulation Of Type 1 Diabetes, James Edward Carter Iii
Loma Linda University Electronic Theses, Dissertations & Projects
Type 1 diabetes mellitus (T1D) is a debilitating chronic inflammatory disease of the insulin-producing pancreatic islet β-cells that results from a combination of genetic and environmental factors. Attempts to suppress Th1-mediated autoimmune diseases such as T1D by mucosal delivery of autoantigens for immunotolerization have yielded only partial success. Attainment of satisfactory levels of sustained immunological tolerance remains to be accomplished. To restore self-tolerance requires delivery of sufficient amounts of autoantigen to stimulate regulatory T helper cells that function to survey the gut and induce tolerance to consumed antigens such as food. Oral delivery of autoantigens has previously been shown to …