The structure of the RNA-dependent RNA polymerase from bovine viral diarrhea virus establishes the role of GTP in de novo initiation.
Kyung H. Choi,James M. Groarke,James M. Groarke,Dorothy C. Young,Richard J. Kuhn,Janet L. Smith,Daniel C. Pevear,Michael G. Rossmann +7 more
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The structure of BVDV polymerase complexed with GTP, which is required for de novo (primer-independent) initiation, shows that GTP binds adjacent to the initiation NTP, suggesting that the GTP mimics aigial RNA product.Abstract:
The bovine viral diarrhea virus (BVDV) RNA-dependent RNA polymerase can initiate RNA replication by a de novo mechanism without a primer. The structure of BVDV polymerase, determined to 2.9-A resolution, contains a unique N-terminal domain, in addition to the fingers, palm, and thumb domains common to other polymerases. The structure of BVDV polymerase complexed with GTP, which is required for de novo (primer-independent) initiation, shows that GTP binds adjacent to the initiation NTP, suggesting that the GTP mimics a vestigial RNA product. Comparison of five monomers in two different crystal forms showed conformational changes in the fingertip region and in the thumb domain that may help to translocate the RNA template and product strands during elongation. The putative binding sites of previously reported BVDV inhibitors are also discussed.read more
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Flaviviridae :T he Viruses and Their Replication
TL;DR: The present research attacked the Flavivirus infection through two mechanisms: Membrane Reorganization and the Compartmentalization and Assembly and Release of Particles from Flaviv virus-infected Cells and Host Resistance to Flaviviral Infection.
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Short protocols in molecular biology
TL;DR: Current Protocols in Molecular Biology Title NLM.
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Crystal Structure of the Dengue Virus RNA-Dependent RNA Polymerase Catalytic Domain at 1.85-Angstrom Resolution
Thai Leong Yap,T. Xu,Yen Liang Chen,Hélène Malet,Marie-Pierre Egloff,Bruno Canard,Subhash G. Vasudevan,Julien Lescar,Julien Lescar +8 more
TL;DR: The structure of the NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains and reveals the presence of two zinc ion binding motifs, which should inform and accelerate the structure-based design of antiviral compounds against dengue virus.
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Structure and function of flavivirus NS5 methyltransferase.
Yangsheng Zhou,Debashish Ray,Yiwei Zhao,Hongping Dong,Suping Ren,Suping Ren,Zhong Li,Yi Guo,Kristen A. Bernard,Kristen A. Bernard,Pei Yong Shi,Pei Yong Shi,Hongmin Li,Hongmin Li +13 more
TL;DR: The results demonstrate that the N-7 methylation activity is essential for the WNV life cycle and, thus, methyltransferase represents a novel target for flavivirus therapy.
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Structure and functionality in flavivirus NS-proteins: Perspectives for drug design
Michela Bollati,Karin Alvarez,Rene Assenberg,Cécile Baronti,Bruno Canard,Shelley Cook,Bruno Coutard,Etienne Decroly,Xavier de Lamballerie,Ernest A. Gould,Gilda Grard,Jonathan M. Grimes,Rolf Hilgenfeld,Anna M. Jansson,Hélène Malet,Erika J. Mancini,Eloise Mastrangelo,Andrea Mattevi,Mario Milani,Gregory Moureau,Johan Neyts,Raymond J. Owens,Jingshan Ren,Barbara Selisko,Silvia Speroni,Holger Steuber,David I. Stuart,Torsten Unge,Martino Bolognesi +28 more
TL;DR: Structural and functional aspects emerging from the characterization of two main components (NS3 and NS5 proteins) of the flavivirus replication complex are reviewed to shed light on the design and development of antiviral drug leads.
References
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Book ChapterDOI
Processing of X-ray diffraction data collected in oscillation mode
Zbyszek Otwinowski,Wladek Minor +1 more
TL;DR: The methods presented in the chapter have been applied to solve a large variety of problems, from inorganic molecules with 5 A unit cell to rotavirus of 700 A diameters crystallized in 700 × 1000 × 1400 A cell.
Journal ArticleDOI
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination
Axel T. Brunger,Axel T. Brunger,Paul D. Adams,G M Clore,W. L. DeLano,Piet Gros,R.W. Grosse-Kunstleve,R.W. Grosse-Kunstleve,Jiansheng Jiang,J. Kuszewski,Michael Nilges,Navraj S. Pannu,Randy J. Read,Luke M. Rice,Thomas Simonson,Gregory L. Warren +15 more
TL;DR: The Crystallography & NMR System (CNS) as mentioned in this paper is a software suite for macromolecular structure determination by X-ray crystallography or solution nuclear magnetic resonance (NMR) spectroscopy.
Journal ArticleDOI
Improved methods for building protein models in electron density maps and the location of errors in these models.
TL;DR: In this paper, the authors describe strategies and tools that help to alleviate this problem and simplify the model-building process, quantify the goodness of fit of the model on a per-residue basis and locate possible errors in peptide and side-chain conformations.
Journal ArticleDOI
AMoRe: an automated package for molecular replacement
TL;DR: In this paper, a new molecular-replacement package is presented, which is an improvement on conventional methods, based on more powerful algorithms and a new conception that enables automation and rapid solution.
Journal ArticleDOI
Automated MAD and MIR structure solution
TL;DR: A fully automated procedure for solving MIR and MAD structures has been developed using a scoring scheme to convert the structure-solution process into an optimization problem.