Biochemistry, Biophysics, and Structural Biology 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.

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

Larry Masterson

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 …

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 …

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.

Biodepollution Of Wastewater Containing Phenolic Compounds From Leather Industry By Plant Peroxidases, Mamounata Diao, Nafissetou Ouedraogo, Lamine Baba-Moussa, Paul W. Savadogo, Georges N'Guessan Amani, Mamoudou H. Dicko Prof.

Pr. Mamoudou H. DICKO, PhD

This study deals with the use of peroxidases (POXs) from Allium sativum, Ipomoea batatas, Raphanus sativus and Sorghum bicolor to catalyze the degradation of free phenolic compounds as well as phenolic compounds contained in wastewater from leather industry. Secretory plant POXs were able to catalyze the oxidation of gallic acid, ferulic acid, 4-hydroxybenzoic acid, pyrogallol and 1,4-tyrosol prepared in ethanol 2% (v:v). Efficiency of peroxidase catalysis depends strongly on the chemical nature of phenolic substrates and on the botanical source of the enzymes. It appeared that POX from Raphanus sativus had the highest efficiency. Results show that POXs can also …

A Novel Zinc Binding System, Zevab, Is Critical For Survival Of Nontypeable Haemophilus Influenzae In A Murine Lung Infection Model., José Argüello, Charles Rosadini, Jeffery Gawronski, Daniel Raimunda, Brian Akerley

José M. Argüello

Nontypeable Haemophilus influenzae (NTHI) is a Gram-negative bacterial pathogen that causes upper and lower respiratory infections. Factors required for pulmonary infection by NTHI are not well understood. Previously, using high-throughput insertion tracking by deep sequencing (HITS), putative lung colonization factors were identified. Also, previous research indicates that secreted disulfide-dependent factors are important for virulence of H. influenzae. In the present study, HITS data were compared with an informatics-based list of putative substrates of the periplasmic oxidoreductase DsbA to find and characterize secreted virulence factors. This analysis resulted in identification of the "zinc binding essential for virulence" (zev) locus consisting of …

Chloroplast Phenomics: Systematic Phenotypic Screening Of Chloroplast Protein Mutants In Arabidopsis, Yan Lu, Linda Savage, Robert Last

Yan Lu

No abstract provided.

Evolution Of Domain Co-Occurrences: Some Striking Results, Arli A. Parikesit, Peter F. Stadler, Sonja J. Prohaska

Arli A Parikesit

No abstract provided.