Biochemistry Commons^™

Further Evidence That Geometries Of Fungicides And Pores In Fungal Wall Must Be Compatible To Show Bioavailability / Herman Gershon, Muriel Gershon, And Donald D. Clark Harding Laboratory, The New York Botanical Garde, Fordham University, Bronx, New York 10458, Usa, Herman Gershon, Muriel Gershon, Donald Dudley Clarke Phd

Chemistry Faculty Publications

Copper(II) biscomplexes of 3-bromo-6-chloro-8- quinolinol and 6-bromo-3-chloro-8-quinolinol were prepared, the long axes ofwhich were 16.8 A and 17.6 A respectively. The long axes of the pores in the walls of the test fungi were determined: A niger (15.0 A), A. oryzae (16.8 A), M verrucaria (17.4 A), T viride (15.0 A). M circinelloides (not determined), and T mentagrophytes (11 .4 A). When the long axis of the copper(II) complex was was shorter or equal to that of the pore, there was fungitoxicity. When the long axis of the complex was longer than that of the pore in the fungal wall …

Linking Ligand-Induced Alterations In Androgen Receptor Structure To Differential Gene Expression: A First Step In The Rational Design Of Selective Androgen Receptor Modulators, Dmitri Kazmin, Tatiana Prytkova, C. Edgar Cook, Russell Wolfinger, Tzu-Ming Chu, David Beratan, J. D. Norris, Ching-Yi Chang, Donald P. Mcdonnell

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We have previously identified a family of novel androgen receptor (AR) ligands that, upon binding, enable AR to adopt structures distinct from that observed in the presence of canonical agonists. In this report, we describe the use of these compounds to establish a relationship between AR structure and biological activity with a view to defining a rational approach with which to identify useful selective AR modulators. To this end, we used combinatorial peptide phage display coupled with molecular dynamic structure analysis to identify the surfaces on AR that are exposed specifically in the presence of selected AR ligands. Subsequently, we …

Heparin Modulates The 99-Loop Of Factor Ixa: Effects On Reactivity With Isolated Kunitz-Type Inhibitor Domains, Pierre F. Neuenschwander, Stephen R. Williamson, Armen Nalian, Kimberly J. Baker-Deadmond

Faculty Publications

Reactivity of factor IXa with basic pancreatic trypsin inhibitor is enhanced by low molecular weight heparin (enoxaparin). Previous studies by us have suggested that this effect involves allosteric modulation of factor IXa. We examined the reactivity of factor IXa with several isolated Kunitz-type inhibitor domains: basic pancreatic trypsin inhibitor, the Kunitz inhibitor domain of protease Nexin-2, and the first two inhibitor domains of tissue factor pathway inhibitor. We find that enhancement of factor IXa reactivity by enoxaparin is greatest for basic pancreatic trypsin inhibitor (>10-fold), followed by the second tissue factor pathway inhibitor domain (1.7-fold) and the Kunitz inhibitor …

Exchange Coupling And Contribution Of Induced Orbital Angular Momentum Of Low-Spin Fe^3+ Ions To Magnetic Anisotropy In Cyanide-Bridged Fe2m2 Molecular Magnets: Spin-Polarized Density-Functional Calculations, Stephen Holmes, Kyungwha Park

Chemistry & Biochemistry Faculty Works

Electronic structure and intramolecular exchange constants are calculated for three cyanide-bridged molecular magnets, [Tp⋆FeIII(CN)3MII(DMF)4]2(OTf)2∙2DMF (MII=Mn,Co,Ni) (abbreviated as Fe2Mn2, Fe2Co2, and Fe2Ni2) that have been recently synthesized, within a generalized-gradient approximation in spin-polarized density-functional theory (DFT). Here Tp⋆=[C3(CH3)2HN2]3BH, OTf=O3SCF3, and DMF=HCON(CH3)2. Due to strong ligand fields present in the [Tp⋆FeIII(CN)3]− units, the Fe3+ ions exhibit a low ground-state spin of S=1/2. Our calculations show that the metal ions in the Fe2Mn2 molecule interact antiferromagnetically via cyanide ligands, while those in the Fe2Co2 and Fe2Ni2 molecule interact ferromagnetically. The calculations also suggest that the smallest gaps between the highest occupied molecular orbital …

Direct Control Of Cell Cycle Gene Expression By Proto-Oncogene Product Actr, And Its Autoregulation Underlies Its Transforming Activity, Maggie C. Louie, Alexey S. Revenko, June X. Zou, Jennifer Yao, Hong-Wu Chen

Collected Faculty Scholarship

ACTR (also called AIB1 and SRC-3) was identified as a coactivator for nuclear receptors and is linked to multiple types of human cancer due to its frequent overexpression. However, the molecular mechanism of ACTR oncogenicity and its function independent of nuclear receptors remain to be defined. We demonstrate here that ACTR is required for both normal and malignant human cells to effectively enter S phase. RNA interference-mediated depletion and chromatin immunoprecipitation assays show that endogenous ACTR directly controls the expression of genes important for initiation of DNA replication, which include cdc6, cdc25A, MCM7, cyclin E, and Cdk2. Moreover, consistent with …

Monosaccharide Interactions With Rh(Iii) Cis-Bipyridine Complexes, Sarah M. Lane

Undergraduate Review

No abstract provided.

Nutrient Control Of Microbial Carbon Cycling Along An Ombrotrophicminerotrophic Peatland Gradient, Jason K. Keller, Angela K. Bauers, Scott D. Bridgham, Laurie E. Kellogg, Colleen M. Iversen

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Future climate change and other anthropogenic activities are likely to increase nutrient availability in many peatlands, and it is important to understand how these additional nutrients will influence peatland carbon cycling. We investigated the effects of nitrogen and phosphorus on aerobic CH4 oxidation, anaerobic carbon mineralization (as CO2 and CH4 production), and anaerobic nutrient mineralization in a bog, an intermediate fen, and a rich fen in the Upper Peninsula of Michigan. We utilized a 5-week laboratory nutrient amendment experiment in conjunction with a 6-year field nutrient fertilization experiment to consider how the relative response to nitrogen and phosphorus differed among …

Critical Evaluation Of The Claims Made By Pharmaceutical Companies In Drug Promotional Material In Pakistan, Dileep Kumar Rohra, Anwarul Hassan Gilani, Ismail Kamal Memon, Ghazala Perven, Muhammad Talha Khan, Hina Zafar, Rakesh Kumar

Department of Biological & Biomedical Sciences

Background: In Pakistan, there is no mechanism to monitor the drug promotional campaign by pharmaceutical industry despite the fact that there is enough evidence that irrational pharmacotherapy is increasingly encountered even in the developed countries due to unethical practices of pharmaceutical promotion. Objectives. To audit the drug promotional claims made by the pharmaceutical companies in Pakistan.
Methods: Drug promotional pamphlets and brochures containing claims for the drugs, which were circulated by the pharmaceuticalrepresentatives were collected from 122 general practitioners (GPs) from Karachi and Larkana cities of the Sindh Province. The claims were critically analyzed and audited with the help of …

[3120+1kbdel86kb]+[Pn1303k] Genotype In An Emirati Cystic Fibrosis Patient: Indication Of A Founder Mutation In Palestinian Arabs, Danish Saleheen, Philippe M. Frossard, Emmanuelle Girodon

Department of Biological & Biomedical Sciences

Cystic fibrosis (CF) is the most common life-limiting autosomal recessive disorder in Caucasian population. The disease was initially considered to be rare in Middle Eastern countries. 95% of CF in Emirati families is due to two mutations only--p.S549R(T > G) and p.F508del. We report here the case of a patient referred to CF and Respiratory Clinic at Tawam Hospital for cystic fibrosis transmembrane regulator (CFTR) gene screening to ascertain the diagnosis of CF, who was found to carry a unique genotype, signifying the importance of retrieving ancestral histories of patients with monogenic disorders.

Hiv-1 Subtype A Infection In A Community Of Intravenous Drug Users In Pakistan, Saeed Khan, Mohammad A. Rai, Mohammad R. Khanani, Muhammad N. Khan, Syed H. Ali

Department of Biological & Biomedical Sciences

Background: Data on the subtypes of HIV in a population help in predicting the potential foci of epidemic, tracking the routes of infection and following the patterns of the virus' genetic divergence. Globally, the most prevalent HIV infection is the HIV-1 subtype C. In Asia, predominant subtypes of HIV-1 are B, C, and CRF-01AE. During the last few years, HIV prevalence in Pakistan has taken the form of a concentrated epidemic in at least two high risk groups, namely, Intravenous Drug Users (IDUs) and Male Sex Workers (MSWs). Factors that have facilitated the proliferation of HIV infection include transmission through …

Fluorescent Analysis Of Translesion Dna Synthesis By Using A Novel, Non-Natural Nucleotide Analogue, Irene Lee, Anthony J. Berdis

Chemistry Faculty Publications

The replication of damaged DNA is a promutagenic process that can lead to disease development. This report evaluates the dynamics of nucleotide incorporation opposite an abasic site, a commonly formed DNA lesion, by using two fluorescent nucleotide analogues, 2-aminopurine deoxyribose triphosphate (2-APTP) and 5-phenylindole deoxyribose triphosphate (5-PhITP). In both cases, the kinetics of incorporation were compared by using a 32 P-radiolabel extension assay versus a fluorescence-quenching assay. Although 2-APTP is efficiently incorporated opposite a templating nucleobase (thymine), the kinetics for incorporation opposite an abasic site are significantly slower. The lower catalytic efficiency hinders its use as a probe to study …

Recent Developments Inthe Mechanistic Enzymology Of The Atp-Dependent Lon Protease From Escherichia Coli: Highlights From Kinetic Studies, Irene Lee, Anthony J. Berdis, Carolyn K. Suzuki

Chemistry Faculty Publications

Lon protease, also known as protease La, is one of the simplest ATP-dependent proteases that plays vital roles in maintaining cellular functions by selectively eliminating misfolded, damaged and certain short-lived regulatory proteins. Although Lon is a homo-oligomer, each subunit of Lon contains both an ATPase and a protease active site. This relatively simple architecture compared to other hetero-oligomeric ATP-dependent proteases such as the proteasome makes Lon a useful paradigm for studying the mechanism of ATP-dependent proteolysis. In this article, we survey some recent developments in the mechanistic characterization of Lon with an emphasis on the utilization of pre-steady-state enzyme kinetic …

Sequential Processing Of A Mitochondrial Tandem Protein: Insights Into Protein Import In Schizosaccharomyces Pombe, Oleh Khalimonchuk, Martin Ott, Soledad Funes, Kai Ostermann, Gerhard Rödel, Johannes M. Herrmann

Department of Biochemistry: Faculty Publications

The sequencing of the genome of Schizosaccharomyces pombe revealed the presence of a number of genes encoding tandem proteins, some of which are mitochondrial components. One of these proteins (pre-Rsm22- Cox11) consists of a fusion of Rsm22, a component of the mitochondrial ribosome, and Cox11, a factor required for copper insertion into cytochrome oxidase. Since in Saccharomyces cerevisiae, Cox11 is physically attached to the mitochondrial ribosome, it was suggested that the tandem organization of Rsm22-Cox11 is used to covalently tie the mitochondrial ribosome to Cox11 in S. pombe. We report here that pre-Rsm22-Cox11 is matured in two subsequent …

Development Of Single Nanoparticle Optical Assays For Imaging Single Living Cells, William John Brownlow

Chemistry & Biochemistry Theses & Dissertations

Multi-drug resistance (MDR) has been reported in both prokaryotes and eukaryotes; the pathogenic gram-negative bacteria Pseudomonas aeruginosa can extrude a variety of structurally and functionally diverse substrates via a number of membrane transport systems leading to MDR. We have developed a novel nanoparticle assay to characterize both the membrane transport system composed of the MexAB-OprM efflux pump and the membrane permeability induced by antibiotics. Gold (Au) and silver (Ag) nanoparticles were investigated for use as probes to explore membrane transport in P. aeruginosa.

The surface plasmon absorption (color) of Au nanoparticle solutions was found to change in the presence …

Structural And Thermodynamic Parameters Associated With The Interaction Of Cobalt (Iii) Complexes And Duplex Dna, Jaime M. Ferreira

Seton Hall University Dissertations and Theses (ETDs)

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Never Let Me Clone? Countering An Ethical Argument Against The Reproductive Cloning Of Humans, Yvette Pearson

Philosophy Faculty Publications

In the March 2006 issue of EMBO reports, Christof Tannert, a bioethicist at the Max Delbrück Research Centre in Berlin, Germany, presented a moral argument against human reproductive cloning on the basis of Immanuel Kant’s categorical imperative (Tannert, 2006). In this article, I address some problems with Tannert’s views and show that our concerns about this prospective procedure should prompt us to scrutinize carefully the conventional procreative practices and attitudes. Indeed, if we set aside objections that are grounded in genetic determinism, many of the offensive features of human cloning are identical to problems with procreation by more conventional means, …

2-Aminoethoxydiphenyl Borate As A Prototype Drug For A Group Of Structurally Related Calcium Channel Blockers In Human Platelets, Yuliya Dobrydneva, Christopher J. Abelt, Beth Dovel, Celina M. Thadigiri, Roy L. Williams, Peter F. Blackmore

Chemistry & Biochemistry Faculty Publications

We have synthesized a series of 2-aminoethoxydiphenyl borate (2-APB, 2,2-diphenyl-1,3,2-oxazaborolidine) analogs and tested their ability to inhibit thrombin-induced Ca²⁺ influx in human platelets. The analogs were either synthesized by adding various substituents to the oxazaborolidine ring (methyl, dimethyl, tert-butyl, phenyl, methyl phenyl, and pyridyl) or increasing the size of the oxazaborolidine ring to seven- and nine-membered rings. NMR analysis of the boron-containing analogs suggests that each of them exist as a ring structure through the formation of an N -> B coordinate bond (except for the hexyl analog). The possibility that these boron-containing compounds formed dimers was also …

Intercellular Spreading Of Porphyromonas Gingivalis Infection In Primary Gingival Epithelial Cells, Özlem Yilmaz, Philippe Verbeke, Richard J. Lamont, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Porphyromonas gingivalis, an important periodontal pathogen, is an effective colonizer of oral tissues. The organism successfully invades, multiplies in, and survives for extended periods in primary gingival epithelial cells (GECs). It is unknown whether P. gingivalis resides in the cytoplasm of infected cells throughout the infection or can spread to adjacent cells over time. We developed a technique based on flow cytofluorometry and fluorescence microscopy to study propagation of the organism at different stages of infection of GECs. Results showed that P. gingivalis spreads cell to cell and that the amount of spreading increases gradually over time. There was a …

I. Comparison Of Translesion Bypass Of Guanine–N2 Monoadducts Of Mitomycin C And Guanine-N7 Monoadducts Of 2,7-Diaminomitosene By T7 Exo-, Klenow Exo-, Eta And Klenow Exo+ Dna Polymerases. Ii. Structure-Based Design, Synthesis, Structure-Conformation And Structure-Activity Relationships Studies Of D-Phe-Pro-D-Arg-P1’-Conh2 Tetrapeptides With Inhibitory Activity For Thrombin., Cristina C. Clement

Dissertations, Theses, and Capstone Projects

The guanine (G)-N² DNA monoadduct of mitomycin C (MC), a cytotoxic anticancer drug, inhibits translesion bypass by DNA polymerases. 2,7-Diaminomitosene (2,7-DAM) is the major metabolite of MC in tumor cells, generated by the reduction of MC. 2,7-DAM alkylates DNA in the cell in situ, forming an adduct at the N7 position of 2'-deoxyguanosine (2,7-DAM-dG) and is noncytotoxic. In part I of this study we tested a potential correlation between the lack of cytotoxicity of 2,7-DAM and the relative ease of bypass of this adduct as compared with the MC adduct. 24-mer and 27-mer templates, adducted at a single …

Purification And Initial Biochemical Characterization Of Atp:Cob(I)Alamin Adenosyltransferase (Eutt) Enzyme Of Salmonella Enterica, Nicole R. Baun, Jorge C. Escalante-Semerena

Department of Biochemistry: Faculty Publications

ATP:cob(I)alamin adenosyltransferase (EutT) of Salmonella

enterica was overproduced and enriched to ~70% homogeneity,

and its basic kinetic parameters were determined. Abundant

amounts of EutT protein were produced, but all of it remained

insoluble. Soluble active EutT protein (~70% homogeneous) was

obtained after treatment with detergent. Under conditions in which

cobalamin (Cbl) was saturating, _Km(ATP) = 10 µM, k_cat = 0.03 s^-1,

and V_max = 54.5 nM min^-1. Similarly, under conditions in which

MgATPwas saturating,K_m(Cbl) = 4.1µM, k_cat = 0.06 s^-1, andV_max= …

Microorganisms Pumping Iron: Anaerobic Microbial Iron Oxidation And Reduction, Karrie A. Weber, Laurie A. Achenbach, John D. Coates

School of Biological Sciences: Faculty Publications

Iron (Fe) has long been a recognized physiological requirement for life, yet for many microorganisms that persist in water, soils and sediments, its role extends well beyond that of a nutritional necessity. Fe(II) can function as an electron source for iron-oxidizing microorganisms under both oxic and anoxic conditions and Fe(III) can function as a terminal electron acceptor under anoxic conditions for iron-reducing microorganisms. Given that iron is the fourth most abundant element in the Earth’s crust, iron redox reactions have the potential to support substantial microbial populations in soil and sedimentary environments. As such, biological iron apportionment has been described …

Characterizing An Rna Aptamer And Binding Studies With Synthetic Porphyrazines, Melanie Bozza

Seton Hall University Dissertations and Theses (ETDs)

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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

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 …

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 …

Analysis Of The Mouse And Human Acyl-Coa Thioesterase (Acot) Gene Clusters Shows That Convergent, Functional Evolution Results In A Reduced Number Of Human Peroxisomal Acots., Mary Hunt, Anna Rautanen, Maria Westin, Thomas Svensson, Stefan Alexson

Articles

The maintenance of cellular levels of free fatty acids and acyl-CoAs, the activated form of free fatty acids, is extremely important as imbalances in lipid metabolism have serious consequences for human health. Acyl-CoA thioesterases (ACOTs) hydrolyze acyl-CoAs to the free fatty acid and CoASH, and thereby have the potential to regulate intracellular levels of these compounds. We have previously identified and characterized a mouse ACOT gene cluster, comprised of six genes that apparently arose by gene duplications, encoding acyl- CoA thioesterases with localizations in cytosol (ACOT1), mitochondria (ACOT2) and peroxisomes (ACOT3-6). However, the corresponding human gene cluster contains only three …

Structure-Function Studies Of The Camp-Dependent Protein Kinase In Vitro And In Intact Cells, Gary Z. Morris

Theses and Dissertations in Biomedical Sciences

There are 518 protein kinase genes in the human genome; this constitutes about 1.7% of all human genes. The cAMP-dependent protein kinase (PKA) serves as the prototypic model for the study of kinases because it contains a conserved catalytic core shared with all eukaryotic kinases, it is the simplest kinase, and it is one of the best-characterized serine/threonine kinases. PKA is ubiquitous in mammals and regulates multiple physiological mechanisms such as the cell cycle, apoptosis, cell motility, energy metabolism, and gene transcription through a well-defined intracellular signaling pathway. While PKA clearly has a central physiological role it is still unclear …

Computer-Assisted Docking Of Flavodoxin With The Atp:Co(I)Rrinoid Adenosyltransferase (Coba) Enzyme Reveals Residues Critical For Protein-Protein Interactions But Not For Catalysis*, Nicole R. Buan, Jorge C. Escalante-Semerena

Department of Biochemistry: Faculty Publications

The activity of the housekeeping ATP:co(I)rrinoid adenosyltransferase (CobA) enzyme of Salmonella enterica sv. Typhimurium is required to adenosylate de novo biosynthetic intermediates of adenosylcobalamin and to salvage incomplete and complete corrinoids from the environment of this bacterium. In vitro, reduced flavodoxin (FldA) provides an electron to generate the co(I)rrinoid substrate in the CobA active site. To understand how CobAand FldA interact, a computer model of aCobA∙FldA complex was generated. This model was used to guide the introduction of mutations into CobA using site-directed mutagenesis and the synthesis of a peptide mimic of FldA. Residues Arg-9 and Arg-165 of CobA …

[Accepted Article Manuscript Version (Postprint)] Identification And Functional Characterization Of Arabidopsis Peroxin4 And The Interacting Protein Peroxin22, Bethany Zolman, Melanie Monroe-Augustus, Illeana Silva, Bonnie Bartel

Biology Department Faculty Works

Peroxins are genetically defined as proteins necessary for peroxisome biogenesis. By screening for reduced response to indole-3-butyric acid, which is metabolized to active auxin in peroxisomes, we isolated an Arabidopsis thaliana peroxin4 (pex4) mutant. This mutant displays sucrose-dependent seedling development and reduced lateral root production, characteristics of plant peroxisome malfunction. We used yeast two-hybrid analysis to determine that PEX4, an apparent ubiquitinconjugating enzyme, interacts with a previously unidentified Arabidopsis protein, PEX22. A pex4 pex22 double mutant enhanced pex4 defects, confirming that PEX22 is a peroxin. Expression of both Arabidopsis genes together complemented yeast pex4 or pex22 mutant defects, whereas expression …

Mechanisms Of Hbo-Induced Neuroprotection In A Neonatal Hypoxia-Ischemia Model, John Winter Calvert

Loma Linda University Electronic Theses, Dissertations & Projects

With an incidence approaching 1/4000 live births and as high as 60% in low birth weight infants, cerebral hypoxia-ischemia during the perinatal period is the single most important cause of acute mortality and chronic disability in newborns. Herein, we tested the hypothesis that following a hypoxic-ischemic insult hyperbaric oxygen (HBO) treatment can restore high energy metabolite levels in the affected regions of the brain and through this increase in energy levels ameliorate the spread of cell death following the insult. We also investigated if an additional mechanism by which HBO affords its neuroprotection is by altering the expression of the …

Process For The Preparation Of Citalopram Intermediate, Aslam A. Malik, Hasan Palandoken, Joy A. Stringer, Dershing Huang, Antonio Romero, Olivier Dapremont

Chemistry and Biochemistry

The present invention provides, inter alia, a novel process for the preparation of Citalopram, a known antidepressant.