| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 274, Issue 9, 5573-5580, February 26, 1999
From the The mosquito-borne dengue viruses are
widespread human pathogens causing dengue fever, dengue hemorrhagic
fever, and dengue shock syndrome, placing 40% of the world's
population at risk with no effective treatment. The viral genome is a
positive strand RNA that encodes a single polyprotein precursor.
Processing of the polyprotein precursor into mature proteins is carried
out by the host signal peptidase and by NS3 serine protease, which requires NS2B as a cofactor. We report here the crystal structure of
the NS3 serine protease domain at 2.1 Å resolution. This structure of
the protease combined with modeling of peptide substrates into the
active site suggests identities of residues involved in substrate recognition as well as providing a structural basis for several mutational effects on enzyme activity. This structure will be useful
for development of specific inhibitors as therapeutics against dengue
and other flaviviral proteases.
Dengue Virus NS3 Serine Protease
CRYSTAL STRUCTURE AND INSIGHTS INTO INTERACTION OF THE ACTIVE
SITE WITH SUBSTRATES BY MOLECULAR MODELING AND STRUCTURAL ANALYSIS
OF MUTATIONAL EFFECTS
, Fels Institute, Temple University,
Philadelphia, Pennsylvania 19140 and the ¶ Department of
Biochemistry and Molecular Biology, University of Kansas Medical
Center, Kansas City, Kansas 66160
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. V. Chernov, S. A. Shiryaev, A. E. Aleshin, B. I. Ratnikov, J. W. Smith, R. C. Liddington, and A. Y. Strongin The Two-component NS2B-NS3 Proteinase Represses DNA Unwinding Activity of the West Nile Virus NS3 Helicase J. Biol. Chem., June 20, 2008; 283(25): 17270 - 17278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Luo, T. Xu, C. Hunke, G. Gruber, S. G. Vasudevan, and J. Lescar Crystal Structure of the NS3 Protease-Helicase from Dengue Virus J. Virol., January 1, 2008; 82(1): 173 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Shiryaev, B. I. Ratnikov, A. E. Aleshin, I. A. Kozlov, N. A. Nelson, M. Lebl, J. W. Smith, R. C. Liddington, and A. Y. Strongin Switching the Substrate Specificity of the Two-Component NS2B-NS3 Flavivirus Proteinase by Structure-Based Mutagenesis J. Virol., May 1, 2007; 81(9): 4501 - 4509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Aleshin, S. A. Shiryaev, A. Y. Strongin, and R. C. Liddington Structural evidence for regulation and specificity of flaviviral proteases and evolution of the Flaviviridae fold Protein Sci., May 1, 2007; 16(5): 795 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Bera, R. J. Kuhn, and J. L. Smith Functional Characterization of cis and trans Activity of the Flavivirus NS2B-NS3 Protease J. Biol. Chem., April 27, 2007; 282(17): 12883 - 12892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Rumyantsev, B. R. Murphy, and A. G. Pletnev A Tick-Borne Langat Virus Mutant That Is Temperature Sensitive and Host Range Restricted in Neuroblastoma Cells and Lacks Neuroinvasiveness for Immunodeficient Mice J. Virol., February 1, 2006; 80(3): 1427 - 1439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Satheshkumar, P. Gayathri, K. Prasad, and H. S. Savithri "Natively Unfolded" VPg Is Essential for Sesbania Mosaic Virus Serine Protease Activity J. Biol. Chem., August 26, 2005; 280(34): 30291 - 30300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wu, A. K. Bera, R. J. Kuhn, and J. L. Smith Structure of the Flavivirus Helicase: Implications for Catalytic Activity, Protein Interactions, and Proteolytic Processing J. Virol., August 15, 2005; 79(16): 10268 - 10277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Li, S. P. Lim, D. Beer, V. Patel, D. Wen, C. Tumanut, D. C. Tully, J. A. Williams, J. Jiricek, J. P. Priestle, et al. Functional Profiling of Recombinant NS3 Proteases from All Four Serotypes of Dengue Virus Using Tetrapeptide and Octapeptide Substrate Libraries J. Biol. Chem., August 5, 2005; 280(31): 28766 - 28774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Chambers, D. A. Droll, Y. Tang, Y. Liang, V. K. Ganesh, K. H. M. Murthy, and M. Nickells Yellow fever virus NS2B-NS3 protease: characterization of charged-to-alanine mutant and revertant viruses and analysis of polyprotein-cleavage activities J. Gen. Virol., May 1, 2005; 86(5): 1403 - 1413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Chappell, T. A. Nall, M. J. Stoermer, N.-X. Fang, J. D. A. Tyndall, D. P. Fairlie, and P. R. Young Site-directed Mutagenesis and Kinetic Studies of the West Nile Virus NS3 Protease Identify Key Enzyme-Substrate Interactions J. Biol. Chem., January 28, 2005; 280(4): 2896 - 2903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Niyomrattanakit, P. Winoyanuwattikun, S. Chanprapaph, C. Angsuthanasombat, S. Panyim, and G. Katzenmeier Identification of Residues in the Dengue Virus Type 2 NS2B Cofactor That Are Critical for NS3 Protease Activation J. Virol., December 15, 2004; 78(24): 13708 - 13716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Nall, K. J. Chappell, M. J. Stoermer, N.-X. Fang, J. D. A. Tyndall, P. R. Young, and D. P. Fairlie Enzymatic Characterization and Homology Model of a Catalytically Active Recombinant West Nile Virus NS3 Protease J. Biol. Chem., November 19, 2004; 279(47): 48535 - 48542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-T. Chiou, C.-C. A. Hu, P.-H. Chen, C.-L. Liao, Y.-L. Lin, and J.-J. Wang Association of Japanese encephalitis virus NS3 protein with microtubules and tumour susceptibility gene 101 (TSG101) protein J. Gen. Virol., October 1, 2003; 84(10): 2795 - 2805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Leung, K. Schroder, H. White, N.-X. Fang, M. J. Stoermer, G. Abbenante, J. L. Martin, P. R. Young, and D. P. Fairlie Activity of Recombinant Dengue 2 Virus NS3 Protease in the Presence of a Truncated NS2B Co-factor, Small Peptide Substrates, and Inhibitors J. Biol. Chem., November 30, 2001; 276(49): 45762 - 45771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ackermann and R. Padmanabhan De Novo Synthesis of RNA by the Dengue Virus RNA-dependent RNA Polymerase Exhibits Temperature Dependence at the Initiation but Not Elongation Phase J. Biol. Chem., October 19, 2001; 276(43): 39926 - 39937. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Matusan, P. G. Kelley, M. J. Pryor, J. C. Whisstock, A. D. Davidson, and P. J. Wright Mutagenesis of the dengue virus type 2 NS3 proteinase and the production of growth-restricted virus J. Gen. Virol., July 1, 2001; 82(7): 1647 - 1656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Yusof, S. Clum, M. Wetzel, H. M. K. Murthy, and R. Padmanabhan Purified NS2B/NS3 Serine Protease of Dengue Virus Type 2 Exhibits Cofactor NS2B Dependence for Cleavage of Substrates with Dibasic Amino Acids in Vitro J. Biol. Chem., March 31, 2000; 275(14): 9963 - 9969. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. You and R. Padmanabhan A Novel in Vitro Replication System for Dengue Virus. INITIATION OF RNA SYNTHESIS AT THE 3'-END OF EXOGENOUS VIRAL RNA TEMPLATES REQUIRES 5'- AND 3'-TERMINAL COMPLEMENTARY SEQUENCE MOTIFS OF THE VIRAL RNA J. Biol. Chem., November 19, 1999; 274(47): 33714 - 33722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. You, B. Falgout, L. Markoff, and R. Padmanabhan In Vitro RNA Synthesis from Exogenous Dengue Viral RNA Templates Requires Long Range Interactions between 5'- and 3'-Terminal Regions That Influence RNA Structure J. Biol. Chem., May 4, 2001; 276(19): 15581 - 15591. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
