Biochemistry Commons^™

A Review Of Baobab (Adansonia Digitata) Products: Effect Of Processing Techniques, Medicinal Properties And Uses, Donatien Kabore, Hagrétou Sawadogo-Lingani, Bréhima Diawara, Clarise Compaoré, Mamoudou H. Dicko Prof., Mogens Jacobsen

Pr. Mamoudou H. DICKO, PhD

A general literature review including the effect of processing techniques, medicinal value and uses of baobab tree is reported in this manuscript. Baobab tree has multi-purpose uses, as it produces food and non-food products such as medicines, fuel, timber, fodder. Every part of the baobab tree is reported to be useful. The seeds, leaves, roots, flowers, fruit pulp and bark of baobab are edible. Baobab leaves are used in the preparation of soup. Seeds are used as a thickening agent in soups, but they can be fermented and used as a flavouring agent or roasted and eaten as snacks. The …

Map Kinases Couple Hindbrain-Derived Catecholamine Signals To Hypothalamic Adrenocortical Control Mechanisms During Glycemia-Related Challenges, Arshad M. Khan, Kimberly L. Kaminski, Graciela Sanchez-Watts, Todd A. Ponzio, J. Brent Kuzmiski, Jaideep S. Bains, Alan G. Watts

Arshad M. Khan, Ph.D.

No abstract provided.

The Occurrence Of A Thylakoid-Localized Small Zinc Finger Protein In Land Plants, Yan Lu

Yan Lu

No abstract provided.

Promise Of Advances In Simulation Methods For Protein Crystallography: Implicit Solvent Models, Time-Averaging Refinement, And Quantum Mechanical Modeling, Celia Schiffer, Jan Hermans

Celia A. Schiffer

No abstract provided.

Competition Between Ski And Creb-Binding Protein For Binding To Smad Proteins In Transforming Growth Factor-Beta Signaling, Weijun Chen, Suvana Lam, Hema Srinath, Celia Schiffer, William Royer, Kai Lin

Celia A. Schiffer

The family of Smad proteins mediates transforming growth factor-beta (TGF-beta) signaling in cell growth and differentiation. Smads repress or activate TGF-beta signaling by interacting with corepressors (e.g. Ski) or coactivators (e.g. CREB-binding protein (CBP)), respectively. Specifically, Ski has been shown to interfere with the interaction between Smad3 and CBP. However, it is unclear whether Ski competes with CBP for binding to Smads and whether they can interact with Smad3 at the same binding surface on Smad3. We investigated the interactions among purified constructs of Smad, Ski, and CBP in vitro by size-exclusion chromatography, isothermal titration calorimetry, and mutational studies. Here, …

Mass Spectrometry Analysis Of Hiv-1 Vif Reveals An Increase In Ordered Structure Upon Oligomerization In Regions Necessary For Viral Infectivity, Jared Auclair, Karin Green, Shivender Shandilya, James Evans, Mohan Somasundaran, Celia Schiffer

Celia A. Schiffer

HIV-1 Vif, an accessory protein in the viral genome, performs an important role in viral pathogenesis by facilitating the degradation of APOBEC3G, an endogenous cellular inhibitor of HIV-1 replication. In this study, intrinsically disordered regions are predicted in HIV-1 Vif using sequence-based algorithms. Intrinsic disorder may explain why traditional structure determination of HIV-1 Vif has been elusive, making structure-based drug design impossible. To characterize HIV-1 Vif's structural topology and to map the domains involved in oligomerization we used chemical cross-linking, proteolysis, and mass spectrometry. Cross-linking showed evidence of monomer, dimer, and trimer species via denaturing gel analysis and an additional …

Viral Protease Inhibitors, Jeffrey Anderson, Celia Schiffer, Sook-Kyung Lee, Ronald Swanstrom

Celia A. Schiffer

This review provides an overview of the development of viral protease inhibitors as antiviral drugs. We concentrate on HIV-1 protease inhibitors, as these have made the most significant advances in the recent past. Thus, we discuss the biochemistry of HIV-1 protease, inhibitor development, clinical use of inhibitors, and evolution of resistance. Since many different viruses encode essential proteases, it is possible to envision the development of a potent protease inhibitor for other viruses if the processing site sequence and the catalytic mechanism are known. At this time, interest in developing inhibitors is limited to viruses that cause chronic disease, viruses …

Mutation Patterns And Structural Correlates In Human Immunodeficiency Virus Type 1 Protease Following Different Protease Inhibitor Treatments, Thomas Wu, Celia Schiffer, Matthew Gonzales, Jonathan Taylor, Rami Kantor, Sunwen Chou, Dennis Israelski, Andrew Zolopa, W. Jeffrey Fessel, Robert Shafer

Celia A. Schiffer

Although many human immunodeficiency virus type 1 (HIV-1)-infected persons are treated with multiple protease inhibitors in combination or in succession, mutation patterns of protease isolates from these persons have not been characterized. We collected and analyzed 2,244 subtype B HIV-1 isolates from 1,919 persons with different protease inhibitor experiences: 1,004 isolates from untreated persons, 637 isolates from persons who received one protease inhibitor, and 603 isolates from persons receiving two or more protease inhibitors. The median number of protease mutations per isolate increased from 4 in untreated persons to 12 in persons who had received four or more protease inhibitors. …

Curling Of Flap Tips In Hiv-1 Protease As A Mechanism For Substrate Entry And Tolerance Of Drug Resistance, Walter Scott, Celia Schiffer

Celia A. Schiffer

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) protease is an essential viral protein that is a major drug target in the fight against Acquired Immune Deficiency Syndrome (AIDS). Access to the active site of this homodimeric enzyme is gained when two large flaps, one from each monomer, open. The flap movements are therefore central to the function of the enzyme, yet determining how these flaps move at an atomic level has not been experimentally possible.

RESULTS: In the present study, we observe the flaps of HIV-1 protease completely opening during a 10 ns solvated molecular dynamics simulation starting from …

Exploring The Role Of The Solvent In The Denaturation Of A Protein: A Molecular Dynamics Study Of The Dna Binding Domain Of The 434 Repressor, Celia Schiffer, Volker Dötsch, Kurt Wuthrich, Wilfred Van Gunsteren

Celia A. Schiffer

Molecular dynamics simulations of the DNA binding domain of 434 repressor are presented which aim at unraveling the role of solvent in protein denaturation. Four altered solvent models, each mimicking various possible aspects of the addition of a denaturant to the aqueous solvent, were used in the simulations to analyze their effects on the stability of the protein. The solvent was altered by selectively changing the Coulombic interaction between water and protein atoms and between different water molecules. The use of a modified solvent model has the advantage of mimicking the presence of denaturant without having denaturant molecules present in …

Resilience To Resistance Of Hiv-1 Protease Inhibitors: Profile Of Darunavir, Eric Lefebvre, Celia A. Schiffer

Celia A. Schiffer

The current effectiveness of HAART in the management of HIV infection is compromised by the emergence of extensively cross-resistant strains of HIV-1, requiring a significant need for new therapeutic agents. Due to its crucial role in viral maturation and therefore HIV-1 replication and infectivity, the HIV-1 protease continues to be a major development target for antiretroviral therapy. However, new protease inhibitors must have higher thresholds to the development of resistance and cross-resistance. Research has demonstrated that the binding characteristics between a protease inhibitor and the active site of the HIV-1 protease are key factors in the development of resistance. More …

Structural Analysis Of Human Immunodeficiency Virus Type 1 Crf01_Ae Protease In Complex With The Substrate P1-P6., Rajintha Bandaranayake, Moses Prabu-Jeyabalan, Junko Kakizawa, Wataru Sugiura, Celia Schiffer

Celia A. Schiffer

The effect of amino acid variability between human immunodeficiency virus type 1 (HIV-1) clades on structure and the emergence of resistance mutations in HIV-1 protease has become an area of significant interest in recent years. We determined the first crystal structure of the HIV-1 CRF01_AE protease in complex with the p1-p6 substrate to a resolution of 2.8 A. Hydrogen bonding between the flap hinge and the protease core regions shows significant structural rearrangements in CRF01_AE protease compared to the clade B protease structure.

Arabidopsis And Tobacco Superman Regulate Hormone Signalling And Mediate Cell Proliferation And Differentiation, C. Nibau, V. S. Di Stilio, H. M. Wu, Alice Cheung

Alice Cheung

Arabidopsis thaliana superman (SUP) plays an important role during flower development by maintaining the boundary between stamens and carpels in the inner two whorls. It was proposed that SUP maintains this boundary by regulating cell proliferation in both whorls, as loss-of-function superman mutants produce more stamens at the expense of carpels. However, the cellular mechanism that underlies SUP function remains unknown. Here Arabidopsis or tobacco (Nicotiana tabacum) SUP was overexpressed in tobacco plants to substantiate SUP's role as a regulator of cell proliferation and boundary definition and provide evidence that its biological role may be mediated via hormonal changes. It …

Altered Microrna Expression In Frontotemporal Lobar Degeneration With Tdp-43 Pathology Caused By Progranulin Mutations, Jannet Kocerha, Naomi Kouri, Matt Baker, Nicole Finch, Mariely Dejesus-Hernandez, John Gonzalez, Kumaravel Chidamparam, Keith A. Josephs, Bradley F. Boeve, Neill R. Graff-Radford, Julia Crook, Dennis W. Dickson, Rosa Rademakers

Jannet Kocerha

Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disorder that can be triggered through genetic or sporadic mechanisms. MicroRNAs (miRNAs) have become a major therapeutic focus as their pervasive expression and powerful regulatory roles in disease pathogenesis become increasingly apparent. Here we examine the role of miRNAs in FTLD patients with TAR DNA-binding protein 43 pathology (FTLD-TDP) caused by genetic mutations in the progranulin (PGRN) gene.

Results

Using miRNA array profiling, we identified the 20 miRNAs that showed greatest evidence (unadjusted P < 0.05) of dysregulation in frontal cortex of eight FTLD-TDP patients carrying PGRN mutations when compared to 32 FTLD-TDP patients with no apparent genetic abnormalities. Quantitative real-time PCR (qRT-PCR) analyses provided technical validation of the differential expression for 9 of the 20 miRNAs in frontal cortex. Additional qRT-PCR analyses showed that 5 out of 9 miRNAs (miR-922, miR-516a-3p, miR-571, miR-548b-5p, and miR-548c-5p) were also significantly dysregulated (unadjusted P < 0.05) in cerebellar tissue samples of PGRN mutation carriers, consistent with a systemic reduction in PGRN levels. We developed a list of gene targets for the 5 candidate miRNAs and found 18 genes dysregulated in a reported FTLD mRNA study to exhibit anti-correlated miRNA-mRNA patterns in affected cortex and cerebellar tissue. Among the targets is brain-specific angiogenesis inhibitor 3, which was recently identified as an important player in synapse biology.

Conclusions

Our study suggests that miRNAs may contribute to the pathogenesis of FTLD-TDP caused by PGRN mutations and …

Camp-Dependent Protein Kinase A Selects The Excited State Of The Membrane Substrate Phospholamban, Larry R. Masterson

Larry Masterson

Comparative Genomics Yields Insights Into Niche Adaptation Of Plant Vascular Wilt Pathogens, Steven J. Klosterman, Krishna V. Subbarao, Seogchan Kang, Paola Veronese, Scott E. Gold, Bart P. H. J. Thomma, Zehua Chen, Bernard Henrissat, Yong-Hwan Lee, Jongsun Park, Dez J. Barbara, Maria D. Garcia-Pedrajas, Amy Anchieta, Ronnie De Jonge, Parthasarathy Santhanam, Karunakaran Maruthachalam, Zahi Atallah, Stefan G. Amyotte, Zahi Paz, Patrik Inderbitzin, Ryan J. Hayes, David I. Heiman, Sarah Young, Qiandong Zeng, Reinhard Engels, James Galagan, Christina A. Cuomo, Katherine F. Dobinson, Li-Jun Ma

Li-Jun Ma

The vascular wilt fungi Verticillium dahliae and V. albo-atrum infect over 200 plant species, causing billions of dollars in annual crop losses. The characteristic wilt symptoms are a result of colonization and proliferation of the pathogens in the xylem vessels, which undergo fluctuations in osmolarity. To gain insights into the mechanisms that confer the organisms' pathogenicity and enable them to proliferate in the unique ecological niche of the plant vascular system, we sequenced the genomes of V. dahliae and V. albo-atrum and compared them to each other, and to the genome of Fusarium oxysporum, another fungal wilt pathogen. Our analyses …

A Highway For War And Peace: The Secretory Pathway In Plant-Microbe Interactions, Dong Wang, X Dong

Dong Wang

Secretion of proteins and other molecules is the primary means by which a cell interacts with its surroundings. The overall organization of the secretory system is remarkably conserved among eukaryotes, and many of the components have been investigated in detail in animal models. Plant cells, because of their sessile lifestyle, are uniquely reliant on the secretory pathway to respond to changes in their environments, either abiotic, such as the absence of nutrients, or biotic, such as the presence of predators or pathogens. In particular, most plant pathogens are extracellular, which demands a robust and efficient host secretory system directed at …

Self-Assembled Rippling Structure Based On Metal-Elastomer Composite For Tunable Plasmonics, Fang-Tzu Chuang

Fang-Tzu Chuang

We demonstrate that a periodic metallic wavy-structure can be easily fabricated on elastomeric polydymethylsiloxane (PDMS) substrates. The metallic wavy-structures are self-assembly formed by thermal evaporation of Ag on PDMS without any lithography processes. The size of the PDMS substrate with an aspect ratio (the ratio of length to width) higher than 2 are found to be necessary to self-assemble the one-dimensional metallic wavy-structure. The period of the wavy-structure is controllable by varing the thickness of the deposited silver film. The elastomeric- gratings can excite surface plasmon on Ag/air interfaces; the resonant wavelength can be tuned to a range of 3.5% …

A Small Zinc Finger Thylakoid Protein Plays A Role In Maintenance Of Photosystem Ii In Arabidopsis Thaliana, Yan Lu, David Hall, Robert Last

Yan Lu

No abstract provided.

Antimicrobial And Antioxidant Activities Of Essential Oil And Methanol Extract Of Matricaria Chamomilla L. From Djibouti, Fatouma M. Abdoul-Latif, Mohamed Nabil, Prosper Edou, Adwa A. Ali, Samatar O. Djama, Louis-Clément Obamé, Mamoudou H. Dicko Prof.

Pr. Mamoudou H. DICKO, PhD

The essential oil and methanol extracts of Matricaria Chamomilla L. were subjected to screening for their possible antioxidant activity by two complementary test systems, namely 2,2-diphenykpicrylhydrazyl (DPPH) free radical scavenging and β-carotene-linoleic acid assays. BHT was used as positive control in both test systems. In the DPPH test system, the IC50 values of essential oil and methanol extracts were 4.18 and 1.83 μg/ml, respectively. In the β-carotene-linoleic acid system, oxidation was effectively inhibited by M. Chamomilla, the RAA value of essential oil and methanol extracts were 12.69 and 11.37 %, respectively. When compared to BHT, the essential oil and methanol …

Muc4 Modulation Of Ligand-Independent Erbb2 Signaling, Goldi Attias Kozloski

Goldi A Kozloski

The membrane mucin Muc4 is a heterodimer, bi-functional glycoprotein complex that is normally expressed in epithelial tissue. Functional studies on the extracellular mucin subunit of Muc4 have shown that it acts to promote anti-adhesion properties by sterically interfering with cell-cell and cell-matrix interactions and that the extent of this effect is directly associated with the number of tandem repeats on this subunit. Functional studies on the transmembrane subunit of Muc4 have shown that this subunit participates in intracellular signaling through interaction with the receptor tyrosine kinase ErbB2. This role of Muc4 was shown to be mediated by stabilizing the heregulin …

Role Of The Extensin Superfamily In Primary Cell Wall Architecture, Derek T.A. Lamport, Marcia J. Kieliszewski, Yuning Chen, Maura Cannon

Maura Cannon

No abstract provided.

Examining The Conformational Dynamics Of Membrane Proteins In Situ With Site-Directed Fluorescence Labeling, Robert Dempski, Ryan Richards

Robert E. Dempski

Two electrode voltage clamp electrophysiology (TEVC) is a powerful tool to investigate the mechanism of ion transport1 for a wide variety of membrane proteins including ion channels2 , ion pumps3 , and transporters4 . Recent developments have combined site-specific fluorophore labeling alongside TEVC to concurrently examine the conformational dynamics at specific residues and function of these proteins on the surface of single cells. We will describe a method to study the conformational dynamics of membrane proteins by simultaneously monitoring fluorescence and current changes using voltage-clamp fluorometry. This approach can be used to examine the molecular motion of membrane proteins site-specifically …

Micrornas Are Independent Predictors Of Outcome In Diffuse Large B-Cell Lymphoma Patients Treated With R-Chop, Goldi Kozloski

Goldi A Kozloski

Dicarbonyldichloridobis(Trimethylphosphane)Iron(Ii)–Carbonyldichloridotris(Trimethylphosphane)Iron(Ii)–Tetrahydrofuran (1/1/2), Nigam P. Rath, Meghan Stouffer, Matthew K. Janssen, John R. Bleeke

Nigam Rath

Kinetic Characterization Of Salmonella Flik-Flhb Interactions Demonstrates Complexity Of The Type Iii Secretion Substrate-Specificity Switch, Daniel P. Morris, Eric D. Roush, J. Will Thompson, M. Arthur Moseley, James W. Murphy, Jonathan L. Mcmurry

Jonathan McMurry

The bacterial flagellum is a complex macromolecular machine consisting of more than 20000 proteins, most of which must be exported from the cell via a dedicated Type III secretion apparatus. At a defined point in flagellar morphogenesis, hook completion is sensed and the apparatus switches substrate specificity type from rod and hook proteins to filament ones. How the switch works is a subject of intense interest. FIiK and F1hBs play central roles. In the present study, two optical biosensing methods were used to characterize FIiK-F1hB interactions using wild-type and two variant FlhBs from mutants with severe flagellar structural defects. Binding …

The Helicobacter Pylori Anti-Sigma Factor Flgm Is Predominantly Cytoplasmic And Cooperates With The Flagellar Basal Body Protein Flha, Melanie Rust, Sophie Borchert, Eike Niehus, Sarah A. Gripp, Afrodita Bajceta, Jonathan L. Mcmurry, Sebastian Suerbaum, Kelly T. Hughes, Christine Josenhans

Jonathan McMurry

Helicobacter pylori requires flagellar motility and orientation to persist actively in its habitat. A particular feature of flagella in most Helicobacter species including H. pylori is a membraneous flagellar sheath. The anti-sigma factor FlgM of H. pylori is unusual, since it lacks an N-terminal domain present in other FlgM homologs, e.g., FlgM of Salmonella spp., whose regulatory function is intimately coupled to its secretion through the flagellar type III secretion system. The aim of the present study was to characterize the localization and secretion of the short H. pylori FlgM in the presence of a flagellar sheath and to elucidate …

Rac/Rop Gtpases And Auxin Signaling, H. M. Wu, O. Hazak, Alice Cheung, S. Yalovsky

Alice Cheung

Auxin functions as a key morphogen in regulating plant growth and development. Studies on auxin-regulated gene expression and on the mechanism of polar auxin transport and its asymmetric distribution within tissues have provided the basis for realizing the molecular mechanisms underlying auxin function. In eukaryotes, members of the Ras and Rho subfamilies of the Ras superfamily of small GTPases function as molecular switches in many signaling cascades that regulate growth and development. Plants do not have Ras proteins, but they contain Rho-like small G proteins called RACs or ROPs that, like fungal and metazoan Rhos, are regulators of cell polarity …

Chloroplast 2010: A Database For Large-Scale Phenotypic Screening Of Arabidopsis Mutants, Yan Lu, Linda Savage, Matthew Larson, Curtis Wilkerson, Robert Last

Yan Lu

No abstract provided.

Localized Shape Resonance On Silver Film Perforated By H-Shaped And More Complex Shaped Hole Arrays, Fang-Tzu Chuang

Fang-Tzu Chuang

The experimental results of light transmission through periodic array of H-shaped hole and more complicated hole which is a combination of multiple U shape are demonstrated. The observations indicate that the localized shape resonance in the longest resonant length of unfolded U-shaped part of the hole always appears. However, localized modes resonant in smaller U-shaped length don't always appear. Localized mode with non-U-shaped resonant path cannot be seen in our sample. In addition, localized mode with different order and resonant path can be excited by different polarized light.