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Articles 31 - 60 of 60

Full-Text Articles in Other Chemistry

Advancing Professional Development Strategies For Chemistry And Biochemistry Undergraduates, Christian A. Brown Apr 2018

Advancing Professional Development Strategies For Chemistry And Biochemistry Undergraduates, Christian A. Brown

Senior Theses

In the Department of Chemistry and Biochemistry at the University of South Carolina (the Department), most curriculum-driven professional development is reserved for third- and fourth-year students. Classroom learning occurs at all levels, but the context comes late. Early exposure to career options and hands-on training is imperative for undergraduates to obtain maximum experiential learning. The purpose of this project is to advance the current professional development strategies of the Department, specifically targeting second- and third-year students. The study surveyed students' current involvement in professional development activities. The data on extracurricular experience and post-graduation interest was used to design a workshop …

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Quantitative Analysis Of Bleomycin In Rat Plasma By Lc-Ms/Ms, Huawen Li Jan 2018

Quantitative Analysis Of Bleomycin In Rat Plasma By Lc-Ms/Ms, Huawen Li

ETD Archive

Bleomycin is the most commonly used compound in its group of antineoplastic drugs. It works on tumor cells by single and double stranded DNA cleavage after its activation, in which it blocks tumor cells’ DNA replication or transcription activities to inhibit tumor cells’ growth. Bleomycin sulfate (Blenoxane) is the most popular preparation used in clinical research, and contains Bleomycin fractions of A2 and B2, which causes difficulties in quantitative analysis. This work uses the metal chelating property of Bleomycin as an advantage to simplify and improve sensitivity of existing quantitative methods. Copper was spiked in excess to plasma samples, followed …

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Functionalization Of Indium-Based Quantum Dots For Use As A Non-Viral Gene Therapy Vector, Nicholas A. Mundt Aug 2017

Functionalization Of Indium-Based Quantum Dots For Use As A Non-Viral Gene Therapy Vector, Nicholas A. Mundt

Graduate Theses/Dissertations

This work aims to develop functionalized, water-soluble indium-based quantum dots (QDs) as a non-viral gene therapy vector. The QDs were solubilized in water by exchanging native hydrophobic surface ligands with 11-mercaptoundecanioc acid (MUA); an amphiphilic ligand providing terminal carboxylate groups that impart water solubility to the QDs. The aqueous QDs were then functionalized with a terminal tertiary amine to impart a positive surface charge, allowing negatively-charged DNA to complex with the nanoparticles. The QDs were characterized via electrophoresis to determine their ability to bind DNA. Results show that further work is needed to optimize DNA binding. In addition, this work …

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Cellular And Molecular Targets Of Menthol Actions, Murat Oz, Eslam El Nebrisi, Keun-Hang Susan Yang, Frank Christopher Howarth, Lina T. Al Kury Jul 2017

Cellular And Molecular Targets Of Menthol Actions, Murat Oz, Eslam El Nebrisi, Keun-Hang Susan Yang, Frank Christopher Howarth, Lina T. Al Kury

Mathematics, Physics, and Computer Science Faculty Articles and Research

Menthol belongs to monoterpene class of a structurally diverse group of phytochemicals found in plant-derived essential oils. Menthol is widely used in pharmaceuticals, confectionary, oral hygiene products, pesticides, cosmetics, and as a flavoring agent. In addition, menthol is known to have antioxidant, anti-inflammatory, and analgesic effects. Recently, there has been renewed awareness in comprehending the biological and pharmacological effects of menthol. TRP channels have been demonstrated to mediate the cooling actions ofmenthol. There has been new evidence demonstrating thatmenthol can significantly influence the functional characteristics of a number of different kinds of ligand and voltage-gated ion channels, indicating that at …

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Conservative Tryptophan Mutations In Protein Tyrosine Phosphatase Ptp1b And Its Effect On Catalytic Rate And Chemical Reaction, Teisha Richan May 2017

Conservative Tryptophan Mutations In Protein Tyrosine Phosphatase Ptp1b And Its Effect On Catalytic Rate And Chemical Reaction, Teisha Richan

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Protein-tyrosine phosphatases (PTPs) catalyze the hydrolysis of phosphorylated tyrosines by a 2-step mechanism involving nucleophilic attack by cysteine and general acid catalysis by aspartic acid. In most PTPs the aspartic acid resides on a flexible protein loop, consisting of about a dozen residues, called the WPD loop. PTP catalysis rates span several orders of magnitude, and differences in WPD loop dynamics have recently been show to correlate with the rate of enzymatic catalysis. The rate of WPD loop motion could possibly be related to a widely conserved tryptophan residue on the WPD loop. Therefore, point mutants were made in PTP1B …

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Phage Display To Identify Functional Resistance Mutations To Rigosertib, Nedim Filipovic Jan 2017

Phage Display To Identify Functional Resistance Mutations To Rigosertib, Nedim Filipovic

CMC Senior Theses

In vitro protein selection has had major impacts in the field of protein engineering. Traditional screens assay individual proteins for specific function. Selection, however, analyzes a pool of mutants and yields the best variants. Phage display, a successful selection technique, also provides a reliable link between variant phenotype and genotype. It can also be coupled with high throughput sequencing to map protein mutations; potentially highlighting vital mutations in variants. We propose to apply this technique to cancer therapy. RAF, a serine/threonine kinase, is critical for cell regulation in mammals. RAF can be activated by oncogenic RAS, found in over 30% …

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Specific Binding Affinity Of The Non-Catalytic Domain Of Eukaryotic Like Type Ib Topoisomerase Of Vaccinia Virus, Benjamin R. Reed Sep 2016

Specific Binding Affinity Of The Non-Catalytic Domain Of Eukaryotic Like Type Ib Topoisomerase Of Vaccinia Virus, Benjamin R. Reed

Dissertations, Theses, and Capstone Projects

Topoisomerases are ubiquitous proteins that alter supercoiling in double stranded DNA (dsDNA) during transcription and replication and. vaccinia and the closely related poxvirus variola virus, at 314 amino acids in length, encode the smallest of the type I topoisomerases(TopIB). TopIB is a two domain protein that recognizes the sequence 5’-T/CCCTT, cleaves at the 3’-end and relaxes supercoiling through rotation. The C-terminal domain (CTD) alone contains the catalytic activity and specificity. Deletion of the N-terminal domain results in a greatly reduced rate of relaxation and rapid dissociation. Biochemical data suggests that the N-terminal domain (NTD) is important for pre-cleavage binding and …

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Interaction Of Spliceosomal U2 Snrnp Protein P14 With Its Branch Site Rna Target, William Perea Vargas Jun 2016

Interaction Of Spliceosomal U2 Snrnp Protein P14 With Its Branch Site Rna Target, William Perea Vargas

Dissertations, Theses, and Capstone Projects

Newly transcribed precursor messenger RNA (pre-mRNA) molecules contain coding sequences (exons) interspersed with non-coding intervening sequences (introns). These introns must be removed in order to generate a continuous coding sequence prior to translation of the message into protein. The mechanism through which these introns are removed is known as pre-mRNA splicing, a two-step reaction catalyzed be a large macromolecular machine, the spliceosome, located in the nucleus of eukaryotic cells. The spliceosome is a protein-directed ribozyme composed of small nuclear RNAs (snRNA) and hundreds of proteins that assemble in a very dynamic process. One of these snRNAs, the U2 snRNA, is …

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The Development Of Colorimetric Assays To Determine The Identity And Frequency Of Specific Nucleobases In Dna Oligomers, Elizabeth Marie Thomas Jan 2016

The Development Of Colorimetric Assays To Determine The Identity And Frequency Of Specific Nucleobases In Dna Oligomers, Elizabeth Marie Thomas

Theses and Dissertations--Chemistry

Colorimetric methods combined with color-changing chemical probes are widely used as simple yet effective tools for identifying and quantifying a wide variety of molecules in solution. For nucleic acids (DNA and RNA), perhaps the most commonly used colorimetric probe is potassium permanganate, which can be used to identify single-stranded pyrimidines (thymine and cytosine) in polymers. Unfortunately, permanganate is not an effective probe for identifying purines (adenine and guanine), especially in the presence of the more reactive pyrimidines. Therefore, robust methods for discriminating between the purines remain elusive, thereby creating a barrier toward developing more complex colorimetric applications. In this dissertation, …

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Investigations Into The Molecular Mechanisms Of Bacterial Pathogen–Host Interactions: Construction Of A Dual Plasmid System For Incorporation Of Unnatural Amino Acids Into Pseudomonas Syringae Pv. Tomato Dc3000, Scotty D. Raber May 2015

Investigations Into The Molecular Mechanisms Of Bacterial Pathogen–Host Interactions: Construction Of A Dual Plasmid System For Incorporation Of Unnatural Amino Acids Into Pseudomonas Syringae Pv. Tomato Dc3000, Scotty D. Raber

Department of Chemistry: Dissertations, Theses, and Student Research

A dual plasmid system for the incorporation of unnatural amino acids into plant pathogen, Pseudomonas syringae pv. tomato DC3000, has been designed. This invention is expected to allow (a) mutations of proteins synthesized by the bacterium, P. syringae pv. tomato DC3000, that can capture molecular targets, especially for such modified proteins secreted by the phytopathogen into the host plant cells of A. thaliana and S. lycopersicum, (b) expression of biological probes in the bacterial species to monitor changes in redox, nutritional, and other small molecule states over pre-, post- and in situ disease stages, and secretion of such biological …

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Sharp Rna Recognition Motif Optimizations, Extensions, And Mutations For Use In 2d And 3d Nmr Experiments, Shaun M. Christie Jan 2015

Sharp Rna Recognition Motif Optimizations, Extensions, And Mutations For Use In 2d And 3d Nmr Experiments, Shaun M. Christie

Williams Honors College, Honors Research Projects

SMRT/HDAC Associated Repressor Protein interacts with the long noncoding RNA, produced by SRA, by binding at the RRMs. Three projects were done to prepare the truncated proteins for use in 2D and 3D NMR experiments. The first focuses on RRM 3 and its optimization during the purification process. The second focuses on RRM 2-4, which was found to be missing two alpha helices that may be important for protein stability. These helices can also interact with RRM 3 as well due to the tight association of RRMs 3 and 4. The two step PCR extension of RRM 2-4 was assumed …

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Revisiting The Fundamentals In The Design And Control Of Nanoparticulate Colloids In The Frame Of Soft Chemistry, Vuk Uskoković Jan 2013

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 …

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Silica As A Matrix For Encapsulating Proteins:Surface Effects On Protein Structure Assessed By Circular Dichroism Spectroscopy, Daryl K. Eggers, P. J. Calabretta, M. C. Chancellor, C. Torres, G. R. Abel Jr., C. Neihaus, N. J. Birtwhistle, N. M. Khouderchah, G. H. Zemede Jan 2012

Silica As A Matrix For Encapsulating Proteins:Surface Effects On Protein Structure Assessed By Circular Dichroism Spectroscopy, Daryl K. Eggers, P. J. Calabretta, M. C. Chancellor, C. Torres, G. R. Abel Jr., C. Neihaus, N. J. Birtwhistle, N. M. Khouderchah, G. H. Zemede

Faculty Publications, Chemistry

The encapsulation of biomolecules in solid materials that retain the native properties of the molecule is a desired feature for the development of biosensors and biocatalysts. In the current study, protein entrapment in silica-based materials is explored using the sol-gel technique. This work surveys the effects of silica confinement on the structure of several model polypeptides, including apomyoglobin, copper-zinc superoxide dismutase, polyglutamine, polylysine, and type I antifreeze protein. Changes in the secondary structure of each protein following encapsulation are monitored by circular dichroism spectroscopy. In many cases, silica confinement reduces the fraction of properly-folded protein relative to solution, but addition …

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Dynamic Light Scattering And Microelectrophoresis: Main Prospects And Limitations, Vuk Uskoković Jan 2012

Dynamic Light Scattering And Microelectrophoresis: Main Prospects And Limitations, Vuk Uskoković

Pharmacy Faculty Articles and Research

Microelectrophoresis based on the dynamic light scattering (DLS) effect has been a major tool for assessing and controlling the conditions for stability of colloidal systems. However, both the DLS methods for characterization of the hydrodynamic size of dispersed submicron particles and the theory behind the electrokinetic phenomena are associated with fundamental and practical approximations that limit their sensitivity and information output. Some of these fundamental limitations, including the spherical approximation of DLS measurements and an inability of microelectrophoretic analyses of colloidal systems to detect discrete charges and differ between differently charged particle surfaces due to rotational diffusion and particle orientation …

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A Bulk Water-Dependent Desolvation Energy Model For Analyzing The Effects Of Secondary Solutes On Biological Equilibria, Daryl K. Eggers Jan 2011

A Bulk Water-Dependent Desolvation Energy Model For Analyzing The Effects Of Secondary Solutes On Biological Equilibria, Daryl K. Eggers

Faculty Publications, Chemistry

A new phenomenological model for interpreting the effects of solutes on biological equilibria is presented. The model attributes changes in equilibria to differences in the desolvation energy of the reacting species that, in turn, reflect changes in the free energy of the bulk water upon addition of secondary solutes. The desolvation approach differs notably from that of other solute models by treating the free energy of bulk water as a variable and by not ascribing the observed shifts in reaction equilibria to accumulation or depletion of solutes next to the surfaces of the reacting species. On the contrary, the partitioning …

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Dynamic Light Scattering And Zeta Potential Of Colloidal Mixtures Of Amelogenin And Hydroxyapatite In Calcium And Phosphate Rich Ionic Milieus, Vuk Uskoković, Roselyn Odsinada, Sonia Djordjevic, Stefan Habelitz Jan 2011

Dynamic Light Scattering And Zeta Potential Of Colloidal Mixtures Of Amelogenin And Hydroxyapatite In Calcium And Phosphate Rich Ionic Milieus, Vuk Uskoković, Roselyn Odsinada, Sonia Djordjevic, Stefan Habelitz

Pharmacy Faculty Articles and Research

The concept of zeta-potential has been used for more than a century as a basic parameter in controlling the stability of colloidal suspensions, irrespective of the nature of their particulate ingredients – organic or inorganic. There are prospects that self-assembly of peptide species and the protein-mineral interactions related to biomineralization may be controlled using this fundamental physicochemical parameter. In this study, we have analyzed the particle size and zeta-potential of the full-length recombinant human amelogenin (rH174), the main protein of the developing enamel matrix, in the presence of calcium and phosphate ions and hydroxyapatite (HAP) particles. As calcium and phosphate …

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Changes In Apparent Molar Water Volume And Dkp Solubility Yield Insights On The Hofmeister Effect, Daryl K. Eggers, A. Y. Payumo, R. M. Huijon, D. D. Mansfield, L. M. Belk, A. K. Bui, A. E. Knight Jan 2011

Changes In Apparent Molar Water Volume And Dkp Solubility Yield Insights On The Hofmeister Effect, Daryl K. Eggers, A. Y. Payumo, R. M. Huijon, D. D. Mansfield, L. M. Belk, A. K. Bui, A. E. Knight

Faculty Publications, Chemistry

This study examines the properties of a 4 × 2 matrix of aqueous cations and anions at concentrations up to 8.0 M. The apparent molar water volume, as calculated by subtracting the mass and volume of the ions from the corresponding solution density, was found to exceed the molar volume of ice in many concentrated electrolyte solutions, underscoring the nonideal behavior of these systems. The solvent properties of water were also analyzed by measuring the solubility of diketopiperazine (DKP) in 2.000 M salt solutions prepared from the same ion combinations. Solution rankings for DKP solubility were found to parallel the …

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Protein Adsorption Onto Organically-Modified Silica Glass Leads To A Different Structure Than Sol-Gel Encapsulation, Daryl K. Eggers, B, Menaa, C. Torres, M. Herrero, V. Rives, A. R.W Gilbert Jan 2008

Protein Adsorption Onto Organically-Modified Silica Glass Leads To A Different Structure Than Sol-Gel Encapsulation, Daryl K. Eggers, B, Menaa, C. Torres, M. Herrero, V. Rives, A. R.W Gilbert

Faculty Publications, Chemistry

The secondary structures of two proteins were examined by circular dichroism spectroscopy after adsorption onto a series of organically modified silica glasses. The glasses were prepared by the sol-gel technique and were varied in hydrophobicity by incorporation of 5% methyl, propyl, trifluoropropyl, or n-hexyl silane. Both cytochrome c and apomyoglobin were found to lose secondary structure after adsorption onto the modified glasses. In the case of apomyoglobin, the α-helical content of the adsorbed protein ranged from 21% to 28%, well below the 62% helix found in solution. In contrast, these same glasses led to a striking increase in apomyoglobin structure …

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Favourable Influence Of Hydrophobic Surfaces On Protein Structure In Porous Organically-Modified Silica Glasses, Daryl K. Eggers, B. Menaa, M. Herrero, V. Rives, M. Lavrenko Jan 2008

Favourable Influence Of Hydrophobic Surfaces On Protein Structure In Porous Organically-Modified Silica Glasses, Daryl K. Eggers, B. Menaa, M. Herrero, V. Rives, M. Lavrenko

Faculty Publications, Chemistry

Organically-modified siloxanes were used as host materials to examine the influence of surface chemistry on protein conformation in a crowded environment. The sol–gel materials were prepared from tetramethoxysilane and a series of monosubstituted alkoxysilanes, RSi(OR′)3, featuring alkyl groups of increasing chain length in the R-position. Using circular dichroism spectroscopy in the far-UV region, apomyoglobin was found to transit from an unfolded state to a native-like helical state as the content of the hydrophobic precursor increased from 0 to 15%. At a fixed molar content of 5% RSi(OR′)3, the helical structure of apomyoglobin increased with the chain length of the R-group, …

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Hydrophobic, Organically-Modified Silica Gels Enhance The Structure Of Encapsulated Apomyoglobin, Daryl K. Eggers, V. A. Rocha Jan 2007

Hydrophobic, Organically-Modified Silica Gels Enhance The Structure Of Encapsulated Apomyoglobin, Daryl K. Eggers, V. A. Rocha

Faculty Publications, Chemistry

Insertion of hydrophobic groups in a silica matrix, by addition of propyl- or trifluoropropyltrimethoxysilane, leads to a surprising increase in the helical content of apomyoglobin following encapsulation by the sol–gel technique

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Dna Damage Responses In Progeroid Syndromes Arise From Defective Maturation Of Prelamin A, Michael Sinensky, Y. Liu, A. Rusinol, Y. Wang, Y. Zou Jan 2006

Dna Damage Responses In Progeroid Syndromes Arise From Defective Maturation Of Prelamin A, Michael Sinensky, Y. Liu, A. Rusinol, Y. Wang, Y. Zou

Faculty Publications, Biological Sciences

The genetic diseases Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) arise from accumulation of farnesylated prelamin A because of defects in the lamin A maturation pathway. Both of these diseases exhibit symptoms that can be viewed as accelerated aging. The mechanism by which accumulation of farnesylated prelamin A leads to these accelerated aging phenotypes is not understood. Here we present evidence that in HGPS and RD fibroblasts, DNA damage checkpoints are persistently activated because of the compromise in genomic integrity. Inactivation of checkpoint kinases Ataxia-telangiectasia-mutated (ATM) and ATR (ATM- and Rad3-related) in these patient cells can partially overcome their …

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Farnesylated Lamins, Progeroid Syndromes And Farnesyl Transferase Inhibitors, Michael Sinensky, A. E. Rusinol Jan 2006

Farnesylated Lamins, Progeroid Syndromes And Farnesyl Transferase Inhibitors, Michael Sinensky, A. E. Rusinol

Faculty Publications, Biological Sciences

Three mammalian nuclear lamin proteins, lamin B1, lamin B2 and the lamin A precursor, prelamin A, undergo canonical farnesylation and processing at CAAX motifs. In the case of prelamin A, there is an additional farnesylation-dependent endoproteolysis, which is defective in two congenital diseases: Hutchinson-Gilford progeria (HGPS) and restrictive dermopathy (RD). These two diseases arise respectively from defects in the prelamin A substrate and the enzyme (ZmpSte24) that processes it. Recent work has shed light on the roles of the lamin proteins and the enzymes involved in their farnesylation-dependent maturation. Other experimental work, including mouse model studies, have examined the possibility …

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Reduced Macrophage Apoptosis Is Associated With Accelerated Atherosclerosis In Low-Denstiy Lipoprotein Receptor-Null Mice, Michael Sinensky, J. Liu, D. P. Thweke, Y. R. Su, M. F. Linton, S. Fazio Jan 2005

Reduced Macrophage Apoptosis Is Associated With Accelerated Atherosclerosis In Low-Denstiy Lipoprotein Receptor-Null Mice, Michael Sinensky, J. Liu, D. P. Thweke, Y. R. Su, M. F. Linton, S. Fazio

Faculty Publications, Biological Sciences

Objective— The majority of apoptotic cells in atherosclerotic lesions are macrophages. However, the pathogenic role of macrophage apoptosis in the development of atherosclerosis remains unclear. Elevated expression of Bax, one of the pivotal proapoptotic proteins of the Bcl-2 family, has been found in human atherosclerotic plaques. Activation of Bax also occurs in free cholesterol-loaded and oxysterol-treated mouse macrophages. In this study, we examined the effect of Bax deficiency in bone marrow-derived leukocytes on the development of atherosclerosis in low-density lipoprotein receptor-null (LDLR−/−) mice. Methods and Results— Fourteen 8-week-old male LDLR−/− mice were lethally irradiated and reconstituted with either wild-type (WT) …

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Familial Als-Associated Mutations Decrease The Thermal Stability Of Distinctly Metallated Species Of Human Copper/Zinc Superoxide Dismutase, Daryl K. Eggers, J. A. Rodriguez, J. S. Valentine, J. A. Roe, A. Tiwari, R. H. Brown, L. J. Hayward Jan 2002

Familial Als-Associated Mutations Decrease The Thermal Stability Of Distinctly Metallated Species Of Human Copper/Zinc Superoxide Dismutase, Daryl K. Eggers, J. A. Rodriguez, J. S. Valentine, J. A. Roe, A. Tiwari, R. H. Brown, L. J. Hayward

Faculty Publications, Chemistry

We report the thermal stability of wild type (WT) and 14 different variants of human copper/zinc superoxide dismutase (SOD1) associated with familial amyotrophic lateral sclerosis (FALS). Multiple endothermic unfolding transitions were observed by differential scanning calorimetry for partially metallated SOD1 enzymes isolated from a baculovirus system. We correlated the metal ion contents of SOD1 variants with the occurrence of distinct melting transitions. Altered thermal stability upon reduction of copper with dithionite identified transitions resulting from the unfolding of copper-containing SOD1 species. We demonstrated that copper or zinc binding to a subset of “WT-like” FALS mutants (A4V, L38V, G41S, G72S, D76Y, …

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Complexes Between Nascent Polypeptides And Their Molecular Chaperones In The Cytosol Of Mammalian Cells, Daryl K. Eggers, W. J. Welch, W. J. Hansen Jan 1997

Complexes Between Nascent Polypeptides And Their Molecular Chaperones In The Cytosol Of Mammalian Cells, Daryl K. Eggers, W. J. Welch, W. J. Hansen

Faculty Publications, Chemistry

Folding of newly synthesized proteins in vivo is believed to be facilitated by the cooperative interaction of a defined group of proteins known as molecular chaperones. We investigated the direct interaction of chaperones with nascent polypeptides in the cytosol of mammalian cells by multiple methods. A new approach using a polyclonal antibody to puromycin allowed us to tag and capture a population of truncated nascent polypeptides with no bias as to the identity of the bound chaperones. In addition, antibodies that recognize the cytosolic chaperones hsp70, CCT (TRiC), hsp40, p48 (Hip), and hsp90 were compared on the basis of their …

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Expression Of Prelamin A Confers Sensitivity Of Dna Biosynthesis To Lovastatin On F9 Teratocarcinoma Cells, Michael Sinensky, T. Mclain, K. Fantle Jan 1994

Expression Of Prelamin A Confers Sensitivity Of Dna Biosynthesis To Lovastatin On F9 Teratocarcinoma Cells, Michael Sinensky, T. Mclain, K. Fantle

Faculty Publications, Biological Sciences

No abstract provided.

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The Processing Pathway Of Prelamin A, Michael Sinensky, K. Fantle, M. Trujillo, T. Mclain, A. Kupfer, M. Dalton Jan 1994

The Processing Pathway Of Prelamin A, Michael Sinensky, K. Fantle, M. Trujillo, T. Mclain, A. Kupfer, M. Dalton

Faculty Publications, Biological Sciences

The conversion of mammalian prelamin A to mature lamin A proceeds through the removal of 18 amino acids from the carboxyl terminus. The initial step in this processing is the isoprenylation of a CAAX box cysteine. This proteolytic event is distinctive for prelamin A among the known prenylated mammalian proteins. Since the carboxyl terminus of prelamin A is removed during maturation, it is not obvious that this protein would undergo the two reactions subsequent to prenylation observed in other CAAX box proteins-the endoproteolytic removal of the carboxyl-terminal 3 amino acids and the subsequent methylation of the now carboxyl-terminal cysteine. To …

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Isoprenylation Is Required For The Processing Of The Lamin A Precursor, Michael Sinensky, L. A. Beck, T. J. Hosick Jan 1990

Isoprenylation Is Required For The Processing Of The Lamin A Precursor, Michael Sinensky, L. A. Beck, T. J. Hosick

Faculty Publications, Biological Sciences

The nuclear lamina proteins, prelamin A, lamin B, and a 70-kD lamina-associated protein, are posttranslationally modified by a metabolite derived from mevalonate. This modification can be inhibited by treatment with (3-R,S)-3-fluoromevalonate, demonstrating that it is isoprenoid in nature. We have examined the association between isoprenoid metabolism and processing of the lamin A precursor in human and hamster cells. Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by mevinolin (lovastatin) specifically depletes endogenous isoprenoid pools and inhibits the conversion of prelamin A to lamin A. Prelamin A processing is also blocked by mevalonate starvation of Mev-1, a CHO cell line auxotrophic for mevalonate. …

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Incorporation Of A Product Of Mevalonic Acid Metabolism Into Proteins Of Chinese Hamster Ovary Nuclei, Michael Sinensky, L. A. Beck, T. Hosick Jan 1988

Incorporation Of A Product Of Mevalonic Acid Metabolism Into Proteins Of Chinese Hamster Ovary Nuclei, Michael Sinensky, L. A. Beck, T. Hosick

Faculty Publications, Biological Sciences

We have examined the nuclear localization of isoprenylated proteins in CHO-K1 cells labeled with [14C]mevalonate. Nuclear proteins of 68, 70, and 74 kD, posttranslationally modified by an isoprenoid, are also components of a nuclear matrix-intermediate filament preparation from CHO cells. Furthermore, the 68-, 70-, and 74-kD isoprenylated polypeptides are immunoprecipitated from cell extracts with two different anti-lamin antisera. Based on exact two-dimensional comigration with lamin B, both from rat liver lamin and CHO nuclear matrix-intermediate filament preparations, and its immunoprecipitation with anti-lamin antisera, we conclude that the 68-kD isoprenylated protein found in nuclei from [14C]mevalonate-labeled CHO cells is lamin B. …

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Adaptative Alteration In Phospholipid Composition Of Plasma Membranes From A Somatic Cell Mutant Defective In The Regulation Of Cholesterol Biosynthesis, Michael Sinensky Jan 1980

Adaptative Alteration In Phospholipid Composition Of Plasma Membranes From A Somatic Cell Mutant Defective In The Regulation Of Cholesterol Biosynthesis, Michael Sinensky

Faculty Publications, Biological Sciences

A somatic cell mutant (CR1) of a Chinese hamster ovary cell (CHO-K1) which has previously been shown to be defective in the regulation of cholesterol biosynthesis accumulates more cholesterol than the parental cell line in plasma membranes. Although such an increase in membrane cholesterol should lead to an increase in the order parameter of these membranes, as measured with an electron spin resonance spin probe, the order parameters of mutant and wild-type plasma membranes are identical--apparently because of an adaptive alteration in membrane phospholipid composition. The phospholipid compositions of mutant and wild-type cell plasma membranes are compared and the mutant …

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