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Full-Text Articles in Medicine and Health Sciences

Common And Distinct Mechanisms Of Different Redox-Active Carcinogens Involved In The Transformation Of Mouse Jb6p+ Cells, Sun Yang, Bobbye J. Misner, Rita Chiu, Frank L. Meyskens Jr. Dec 2007

Common And Distinct Mechanisms Of Different Redox-Active Carcinogens Involved In The Transformation Of Mouse Jb6p+ Cells, Sun Yang, Bobbye J. Misner, Rita Chiu, Frank L. Meyskens Jr.

Pharmacy Faculty Articles and Research

We transformed JB6P+ cells with prolonged intermittent low-dose UVB radiation or prolonged exposure to low-dose H2O2 or CdCl2. Stable transformation was confirmed by an anchorage-independence assay. The JB6P+ transformants formed more colonies (∼six folds) in soft agar as compared to their JB6P+ parent cells and were associated with increased intracellular reactive oxygen species (ROS) levels. Activating protein-1 (AP-1) is a family of transcription factors that are rapidly activated by elevated intracellular ROS levels, and their composition is important in the process of cellular transformation and/or tumor progression. To investigate if carcinogenesis induced by distinct carcinogens was via similar molecular mechanisms …


Phenylalanyl-Trna Synthetase Editing Defects Result In Efficient Mistranslation Of Phenylalanine Codons As Tyrosine, Jiqiang Ling, Srujana S. Yadavalli, Michael Ibba Sep 2007

Phenylalanyl-Trna Synthetase Editing Defects Result In Efficient Mistranslation Of Phenylalanine Codons As Tyrosine, Jiqiang Ling, Srujana S. Yadavalli, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Translational quality control is monitored at several steps, including substrate selection by aminoacyl-tRNA synthetases (aaRSs), and discrimination of aminoacyl-tRNAs by elongation factor Tu (EF-Tu) and the ribosome. Phenylalanyl-tRNA synthetase (PheRS) misactivates Tyr but is able to correct the mistake using a proofreading activity named editing. Previously we found that overproduction of editing-defective PheRS resulted in Tyr incorporation at Phe-encoded positions in vivo , although the misreading efficiency could not be estimated. This raised the question as to whether or not EF-Tu and the ribosome provide further proofreading mechanisms to prevent mistranslation of Phe codons by Tyr. Here we show that, …


An Aminoacyl-Trna Synthetase: Elongation Factor Complex For Substrate Channeling In Archaeal Translation, Corinne D. Hausmann, Mette Praetorius-Ibba, Michael Ibba Sep 2007

An Aminoacyl-Trna Synthetase: Elongation Factor Complex For Substrate Channeling In Archaeal Translation, Corinne D. Hausmann, Mette Praetorius-Ibba, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Translation requires the specific attachment of amino acids to tRNAs by aminoacyl-tRNA synthetases (aaRSs) and the subsequent delivery of aminoacyl-tRNAs to the ribosome by elongation factor 1 alpha (EF-1α). Interactions between EF-1α and various aaRSs have been described in eukaryotes, but the role of these complexes remains unclear. To investigate possible interactions between EF-1α and other cellular components, a yeast two-hybrid screen was performed for the archaeon Methanothermobacter thermautotrophicus. EF-1α was found to form a stable complex with leucyl-tRNA synthetase (LeuRS; KD = 0.7 μ M). Complex formation had little effect on EF-1α activity, but increased the kcat …


Coupling Coherence Distinguishes Structure Sensitivity In Protein Electron Transfer, Tatiana Prytkova, Igor V. Kurnikov, David Beratan Jan 2007

Coupling Coherence Distinguishes Structure Sensitivity In Protein Electron Transfer, Tatiana Prytkova, Igor V. Kurnikov, David Beratan

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Quantum mechanical analysis of electron tunneling in nine thermally fluctuating cytochrome b562 derivatives reveals two distinct protein-mediated coupling limits. A structure-insensitive regime arises for redox partners coupled through dynamically averaged multiple-coupling pathways (in seven of the nine derivatives) where heme-edge coupling leads to the multiple-pathway regime. A structure-dependent limit governs redox partners coupled through a dominant pathway (in two of the nine derivatives) where axial-ligand coupling generates the single-pathway limit and slower rates. This two-regime paradigm provides a unified description of electron transfer rates in 26 ruthenium-modified heme and blue-copper proteins, as well as in numerous photosynthetic proteins.


Flavin Charge Transfer Transitions Assist Dna Photolyase Electron Transfer, Spiros S. Skourtis, Tatiana Prytkova, David Beratan Jan 2007

Flavin Charge Transfer Transitions Assist Dna Photolyase Electron Transfer, Spiros S. Skourtis, Tatiana Prytkova, David Beratan

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

This contribution describes molecular dynamics, semi-empirical and ab-initio studies of the primary photo-induced electron transfer reaction in DNA photolyase. DNA photolyases are FADH−-containing proteins that repair UV-damaged DNA by photo-induced electron transfer. A DNA photolyase recognizes and binds to cyclobutatne pyrimidine dimer lesions of DNA. The protein repairs a bound lesion by transferring an electron to the lesion from FADH−, upon photo-excitation of FADH− with 350–450 nm light. We compute the lowest singlet excited states of FADH− in DNA photolyase using INDO/S configuration interaction, time-dependent density-functional, and time-dependent Hartree-Fock methods. The calculations identify the lowest singlet excited state of FADH− …


The Endogenous Cannabinoid Anandamide Inhibits Cromakalim-Activated K+ Currents In Follicle-Enclosed Xenopus Oocytes, Murat Oz, Keun-Hang Susan Yang, Meral Dinc, Toni S. Shippenberg Jan 2007

The Endogenous Cannabinoid Anandamide Inhibits Cromakalim-Activated K+ Currents In Follicle-Enclosed Xenopus Oocytes, Murat Oz, Keun-Hang Susan Yang, Meral Dinc, Toni S. Shippenberg

Mathematics, Physics, and Computer Science Faculty Articles and Research

The effect of the endogenous cannabinoid anandamide on K+ currents activated by the ATP-sensitive potassium (KATP) channel opener cromakalim was investigated in follicle-enclosed Xenopus oocytes using the two-electrode voltage-clamp technique. Anandamide (1–90 μM) reversibly inhibited cromakalim-induced K+ currents, with an IC50 value of 8.1 ± 2 μM. Inhibition was noncompetitive and independent of membrane potential. Coapplication of anandamide with the cannabinoid type 1 (CB1) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR 141716A) (1 μM), the CB2 receptor antagonist N-[(1S)endo-1,3,3-trimethyl bicyclo heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) (1 μM), or pertussis toxin (5 μg/ml) did not alter the inhibitory effect of anandamide, suggesting that known cannabinoid receptors …


Protein Pyrophosphorylation By Inositol Pyrophosphates Is A Posttranslational Event, Rashna Bhandari, Adolfo Saiardi, Yousef Ahmadibeni, Adele M. Snowman, Adam C. Resnick, Troels Z. Kristiansen, Henrik Molina, Akhilesh Pandey, J. Kent Werner Jr., Krishna R. Juluri, Yong Xu, Glenn D. Prestwich, Keykavous Parang, Solomon H. Snyder Jan 2007

Protein Pyrophosphorylation By Inositol Pyrophosphates Is A Posttranslational Event, Rashna Bhandari, Adolfo Saiardi, Yousef Ahmadibeni, Adele M. Snowman, Adam C. Resnick, Troels Z. Kristiansen, Henrik Molina, Akhilesh Pandey, J. Kent Werner Jr., Krishna R. Juluri, Yong Xu, Glenn D. Prestwich, Keykavous Parang, Solomon H. Snyder

Pharmacy Faculty Articles and Research

In a previous study, we showed that the inositol pyrophosphate diphosphoinositol pentakisphosphate (IP(7)) physiologically phosphorylates mammalian and yeast proteins. We now report that this phosphate transfer reflects pyrophosphorylation. Thus, proteins must be prephosphorylated by ATIP to prime them for IP(7) phosphorylation. IP(7) phosphorylates synthetic phosphopeptides but not if their phosphates have been masked by methylation or pyrophosphorylation. Moreover, IP(7) phosphorylated peptides are more acid-labile and more resistant to phosphatases than ATIP phosphorylated peptides, indicating a different type of phosphate bond. Pyrophosphorylation may represent a novel mode of signaling to proteins.


Synthesis And Antifungal Properties Of Alpha-Methoxy And Alpha-Hydroxyl Substituted 4-Thiatetradecanoic Acids, Nestor Carballeira, Rosann O'Neill, Keykavous Parang Jan 2007

Synthesis And Antifungal Properties Of Alpha-Methoxy And Alpha-Hydroxyl Substituted 4-Thiatetradecanoic Acids, Nestor Carballeira, Rosann O'Neill, Keykavous Parang

Pharmacy Faculty Articles and Research

4-Thiatetradecanoic acid exhibited weak antifungal activities against Candida albicans (ATCC 60193), Cryptococcus neoformans (ATCC 6603 1), and Aspergillus niger (ATCC 16404) (MIC = 4.8-12.7 mM). It has been demonstrated that alpha-methoxylation efficiently blocks P-oxidation and significantly improve the antifungal activities of fatty acids. We examined whether antifungal activity of 4-thiatetradecanoic acid can be improved by a-substitution. The unprecedented (+/-)-2-tiydroxy-4-thiatetradecanoic acid was synthesized in four steps (20% overall yield), while the (+/-)-2-methoxy-4-thiatetradecanoic acid was synthesized in five steps (14% overall yield) starting from 1-decanethiol. The key step in the synthesis was the hydrolysis of a trimethylsilyloxynitrile. In general, the novel (+/-)-2-methoxy-4-thiatetradecanoic …