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Author (up) Dingley, A.J.; Lorenzen, I.; Grotzinger, J. file  url
  Title NMR analysis of viral protein structures Type Journal Article
  Year 2008 Publication Methods in Molecular Biology (Clifton, N.J.) Abbreviated Journal Methods Mol Biol  
  Volume 451 Issue Pages 441-462  
  Keywords Cloning, Molecular; DNA, Complementary; Indicators and Reagents; Magnetic Resonance Spectroscopy--methods; Models, Molecular; Protein Conformation; Recombinant Proteins--chemistry; Solutions; Viral Proteins--chemistry, genetics, isolation & purification  
  Abstract Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool to study the three-dimensional structure of proteins and nucleic acids at atomic resolution. Since the NMR data can be recorded in solution, conditions such as pH, salt concentration, and temperature can be adjusted so as to closely mimic the biomacromolecules natural milieu. In addition to structure determination, NMR applications can investigate time-dependent phenomena, such as dynamic features of the biomacromolecules, reaction kinetics, molecular recognition, or protein folding. The advent of higher magnetic field strengths, new technical developments, and the use of either uniform or selective isotopic labeling techniques, currently allows NMR users the opportunity to investigate the tertiary structure of biomacromolecules of approximately 50 kDa. This chapter will outline the basic protocol for structure determination of proteins by NMR spectroscopy. In general, there are four main stages: (i) preparation of a homogeneous protein sample, (ii) the recording of the NMR data sets, (iii) assignment of the spectra to each NMR observable atom in the protein, and (iv) generation of structures using computer software and the correctly assigned NMR data.  
  Call Number Serial 782  
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Author (up) Ducey, T.F.; Jackson, L.; Orvis, J.; Dyer, D.W. file  url
doi  openurl
  Title Transcript analysis of nrrF, a Fur repressed sRNA of Neisseria gonorrhoeae Type Journal Article
  Year 2009 Publication Microbial Pathogenesis Abbreviated Journal Microb Pathog  
  Volume 46 Issue 3 Pages 166-170  
  Keywords Bacterial Proteins/*physiology; Base Sequence; Escherichia coli; Gene Expression Profiling; *Gene Expression Regulation, Bacterial; Models, Molecular; Molecular Sequence Data; Neisseria gonorrhoeae/*physiology; RNA, Bacterial/*genetics; RNA, Untranslated/*metabolism; Repressor Proteins/*physiology; Transcription Initiation Site  
  Abstract Like most microorganisms, Neisseria gonorrhoeae alters gene expression in response to iron availability. The ferric uptake regulator Fur has been shown to be involved in controlling this response, but the extent of this involvement remains unknown. It is known that in addition to working directly to repress gene expression, Fur may also work indirectly by controlling additional regulatory elements. Using in silico analysis, we identified a putative small RNA (sRNA) homolog of the meningococcal nrrF locus, and demonstrate that this sRNA is iron-repressible, suggesting that this is the gonococcal analog of the rhyB locus in Escherichia coli. Quantitative real-time RT-PCR analysis indicates that this transcript may also be temporally regulated. Transcript analysis identified the 5' start of the transcript, using a single reaction, fluorescent-based, primer extension assay. This protocol allows for the rapid identification of transcriptional start sites of RNA transcripts, and could be used for high-throughput transcript mapping.  
  Call Number Serial 417  
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Author (up) Giles, G.I.; Sharma, R.P. file  url
  Title Topoisomerase enzymes as therapeutic targets for cancer chemotherapy Type Journal Article
  Year 2005 Publication Medicinal Chemistry (Shariqah (United Arab Emirates)) Abbreviated Journal Med Chem  
  Volume 1 Issue 4 Pages 383-394  
  Keywords Antineoplastic Agents/pharmacology/*therapeutic use; Binding Sites; *Drug Delivery Systems; *Drug Therapy; Enzyme Inhibitors/pharmacology/therapeutic use; Humans; Models, Molecular; Neoplasms/*drug therapy; *Topoisomerase I Inhibitors; *Topoisomerase II Inhibitors  
  Abstract The topoisomerase enzymes are essential for DNA metabolism, where they act to adjust the number of supercoils in DNA, a key requirement in the cellular processes of transcription and replication. Their enzymatic mechanism creates transient nicks (type I) or breaks (type II) in the double stranded DNA polymer, allowing DNA to be converted between topological isomers. Humans possess both types of topoisomerase enzymes, however the two types utilize very different enzymatic mechanisms. Both type I and type II topoisomerases have been identified as clinically important targets for cancer chemotherapy and their inhibitors are central components in many therapeutic regimes. Over the course of the last 30 years inhibitors with extensive structural diversity have been developed through a combination of drug screening and rational design programs. Simultaneously much emphasis has been placed upon establishing the mechanisms of action of both classes of topoisomerase enzyme. Crucial structural insights have come from the crystal structure of topoisomerase I, while modelling comparisons are beginning to map out a possible framework for topoisomerase II action. This review discusses these recent advances in the fields of enzyme mechanism and inhibitor design. We also address the development of drug resistance and dose-limiting side effects as well as cover alternative methods in drug delivery.  
  Call Number Serial 200  
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Author (up) Hakkinen, H. file  url
  Title The gold-sulfur interface at the nanoscale Type Journal Article
  Year 2012 Publication Nature Chemistry Abbreviated Journal Nat Chem  
  Volume 4 Issue 6 Pages 443-455  
  Keywords Crystallography, X-Ray; Drug Delivery Systems; Gold/*chemistry; Models, Molecular; *Nanotechnology; Stereoisomerism; Sulfhydryl Compounds/chemistry; Sulfur/*chemistry; Surface Properties  
  Abstract Thiolate-protected gold surfaces and interfaces, relevant for self-assembled monolayers of organic molecules on gold, for passivated gold nanoclusters and for molecule-gold junctions, are archetypal systems in various fields of current nanoscience research, materials science, inorganic chemistry and surface science. Understanding this interface at the nanometre scale is essential for a wide range of potential applications for site-specific bioconjugate labelling and sensing, drug delivery and medical therapy, functionalization of gold surfaces for sensing, molecular recognition and molecular electronics, and gold nanoparticle catalysis. During the past five years, considerable experimental and theoretical advances have furthered our understanding of the molecular structure of the gold-sulfur interface in these systems. This Review discusses the recent progress from the viewpoint of theory and computations, with connections to relevant experiments.  
  Call Number Serial 1238  
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Author (up) Hassaine, G.; Deluz, C.; Grasso, L.; Wyss, R.; Tol, M.B.; Hovius, R.; Graff, A.; Stahlberg, H.; Tomizaki, T.; Desmyter, A.; Moreau, C.; Li, X.-D.; Poitevin, F.; Vogel, H.; Nury, H. file  url
  Title X-ray structure of the mouse serotonin 5-HT3 receptor Type Journal Article
  Year 2014 Publication Nature Abbreviated Journal Nature  
  Volume 512 Issue 7514 Pages 276-281  
  Keywords Amino Acid Sequence; Animals; Binding Sites; Crystallography, X-Ray; Mice; Models, Molecular; Molecular Sequence Data; Neurotransmitter Agents/metabolism; Protein Structure, Quaternary; Protein Structure, Tertiary; Protein Subunits/chemistry/metabolism; Receptors, Serotonin, 5-HT3/*chemistry/metabolism  
  Abstract Neurotransmitter-gated ion channels of the Cys-loop receptor family mediate fast neurotransmission throughout the nervous system. The molecular processes of neurotransmitter binding, subsequent opening of the ion channel and ion permeation remain poorly understood. Here we present the X-ray structure of a mammalian Cys-loop receptor, the mouse serotonin 5-HT3 receptor, at 3.5 A resolution. The structure of the proteolysed receptor, made up of two fragments and comprising part of the intracellular domain, was determined in complex with stabilizing nanobodies. The extracellular domain reveals the detailed anatomy of the neurotransmitter binding site capped by a nanobody. The membrane domain delimits an aqueous pore with a 4.6 A constriction. In the intracellular domain, a bundle of five intracellular helices creates a closed vestibule where lateral portals are obstructed by loops. This 5-HT3 receptor structure, revealing part of the intracellular domain, expands the structural basis for understanding the operating mechanism of mammalian Cys-loop receptors.  
  Call Number Serial 1007  
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Author (up) Iorga, B.; Herlem, D.; Barre, E.; Guillou, C. file  url
  Title Acetylcholine nicotinic receptors: finding the putative binding site of allosteric modulators using the “blind docking” approach Type Journal Article
  Year 2006 Publication Journal of Molecular Modeling Abbreviated Journal J Mol Model  
  Volume 12 Issue 3 Pages 366-372  
  Keywords Allosteric Site; Amino Acid Sequence; Conserved Sequence; Humans; Models, Molecular; Molecular Sequence Data; Protein Structure, Quaternary; Protein Subunits/chemistry/metabolism; Receptors, Nicotinic/*chemistry/*metabolism; Sequence Alignment  
  Abstract Allosteric potentiation of acetylcholine nicotinic receptors is considered to be one of the most promising approaches for the treatment of Alzheimer's disease. However, the exact localization of the allosteric binding site and the potentiation mechanism at the molecular level are presently unknown. We have performed the “blind docking” of three known allosteric modulators (galanthamine, codeine and eserine) with the Acetylcholine Binding Protein and models of human alpha7, alpha3beta4 and alpha4beta2 nicotinic receptors, created by homology modeling. Three putative binding sites were identified in the channel pore, each one showing different affinities for the ligands. One of these sites is localized opposite to the agonist binding site and is probably implicated in the potentiation process. On the basis of these results, a possible mechanism for nicotinic acetylcholine receptor (nAChRs) activation is proposed. The present findings may represent an important advance for understanding the allosteric modulation mechanism of nAChRs. [Figure: see text].  
  Call Number Serial 1889  
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Author (up) Knowles, T.J.; Scott-Tucker, A.; Overduin, M.; Henderson, I.R. file  url
  Title Membrane protein architects: the role of the BAM complex in outer membrane protein assembly Type Journal Article
  Year 2009 Publication Nature Reviews. Microbiology Abbreviated Journal Nat Rev Microbiol  
  Volume 7 Issue 3 Pages 206-214  
  Keywords Bacterial Outer Membrane Proteins--chemistry, metabolism; Escherichia coli Proteins--chemistry, metabolism; Gram-Negative Bacteria--chemistry, metabolism; Models, Molecular; Molecular Chaperones--metabolism; Protein Folding; Protein Multimerization; Protein Transport  
  Abstract The folding of transmembrane proteins into the outer membrane presents formidable challenges to Gram-negative bacteria. These proteins must migrate from the cytoplasm, through the inner membrane and into the periplasm, before being recognized by the beta-barrel assembly machinery, which mediates efficient insertion of folded beta-barrels into the outer membrane. Recent discoveries of component structures and accessory interactions of this complex are yielding insights into how cells fold membrane proteins. Here, we discuss how these structures illuminate the mechanisms responsible for the biogenesis of outer membrane proteins.  
  Call Number Serial 20  
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Author (up) Luger, K.; Mader, A.W.; Richmond, R.K.; Sargent, D.F.; Richmond, T.J. file  url
  Title Crystal structure of the nucleosome core particle at 2.8 A resolution Type Journal Article
  Year 1997 Publication Nature Abbreviated Journal Nature  
  Volume 389 Issue 6648 Pages 251-260  
  Keywords Amino Acid Sequence; Base Composition; Crystallography, X-Ray; DNA/*chemistry; DNA, Superhelical/chemistry; Histones/chemistry; Humans; Models, Molecular; Molecular Sequence Data; Nucleic Acid Conformation; Nucleosomes/*chemistry; Protein Binding; Protein Conformation; Protein Folding  
  Abstract The X-ray crystal structure of the nucleosome core particle of chromatin shows in atomic detail how the histone protein octamer is assembled and how 146 base pairs of DNA are organized into a superhelix around it. Both histone/histone and histone/DNA interactions depend on the histone fold domains and additional, well ordered structure elements extending from this motif. Histone amino-terminal tails pass over and between the gyres of the DNA superhelix to contact neighbouring particles. The lack of uniformity between multiple histone/DNA-binding sites causes the DNA to deviate from ideal superhelix geometry.  
  Call Number Serial 1989  
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Author (up) Narayana, N.; Matthews, D.A.; Howell, E.E.; Nguyen-huu, X. file  url
  Title A plasmid-encoded dihydrofolate reductase from trimethoprim-resistant bacteria has a novel D2-symmetric active site Type Journal Article
  Year 1995 Publication Nature Structural Biology Abbreviated Journal Nat Struct Biol  
  Volume 2 Issue 11 Pages 1018-1025  
  Keywords Amino Acid Sequence; Binding Sites; Crystallography, X-Ray; Folic Acid Antagonists/chemistry/metabolism; Models, Molecular; Molecular Sequence Data; NADP/chemistry/metabolism; Plasmids/*genetics; Protein Conformation; Recombinant Proteins/chemistry; Tetrahydrofolate Dehydrogenase/*chemistry/genetics; Trimethoprim/chemistry/metabolism; Trimethoprim Resistance/*genetics  
  Abstract Bacteria expressing R67-plasmid encoded dihydrofolate reductase (R67 DHFR) exhibit high-level resistance to the antibiotic trimethoprim. Native R67 DHFR is a 34,000 M(r) homotetramer which exists in equilibrium with an inactive dimeric form. The structure of native R67 DHFR has now been solved at 1.7 A resolution and is unrelated to that of chromosomal DHFR. Homotetrameric R67 DHFR has an unusual pore, 25 A in length, passing through the middle of the molecule. Two folate molecules bind asymmetrically within the pore indicating that the enzyme's active site consists of symmetry related binding surfaces from all four identical units.  
  Call Number Serial 1208  
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Author (up) Nicolaou, K.C.; Yang, Z.; Liu, J.J.; Ueno, H.; Nantermet, P.G.; Guy, R.K.; Claiborne, C.F.; Renaud, J.; Couladouros, E.A.; Paulvannan, K. file  url
  Title Total synthesis of taxol Type Journal Article
  Year 1994 Publication Nature Abbreviated Journal Nature  
  Volume 367 Issue 6464 Pages 630-634  
  Keywords Models, Molecular; Molecular Conformation; Paclitaxel/*chemical synthesis/chemistry; Stereoisomerism  
  Abstract Taxol, a substance originally isolated from the Pacific yew tree (Taxus brevifolia) more than two decades ago, has recently been approved for the clinical treatment of cancer patients. Hailed as having provided one of the most significant advances in cancer therapy, this molecule exerts its anticancer activity by inhibiting mitosis through enhancement of the polymerization of tubulin and consequent stabilization of microtubules. The scarcity of taxol and the ecological impact of harvesting it have prompted extension searches for alternative sources including semisynthesis, cellular culture production and chemical synthesis. The latter has been attempted for almost two decades, but these attempts have been thwarted by the magnitude of the synthetic challenge. Here we report the total synthesis of taxol by a convergent strategy, which opens a chemical pathway for the production of both the natural product itself and a variety of designed taxoids.  
  Call Number Serial 1637  
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