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Sars

Sars

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Published by: kwongi on Jan 25, 2009
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12/08/2010

 
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Dimer of SARS Coronavirus Main Proteinase
 
asStudied by Molecular Dynamics Simulations
Vannajan Sanghiran Lee,
a,b
Tawun Remsungnen,
a
Siriporn Promsri,
a
SornthepVannarat,
d
Kitiyaporn Wittayanarakul,
a
Ornjira Aruksakulwong,
a
Vudhichai Parasuk,
a
Pornthep Sompornpisut,
a
Suwipa Saen-oon,
a
Wasun Chantratita,
c
Piyawut Srichaikul,
d
Supot Hannongbua
a,*
a
 Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand 
 b
 Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai50200, Thailand 
c
Virology and Molecular Microbiology, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand 
 High Performance Computing Research and Development Division, National  Electronics and Computer Technology Center, Thailand Science Park, 112 Pahonyothin Road, Klong 1, Klong Luang , Pathumthani 12120, Thailand 
TOTAL PAGE 25TOTAL TABLES 1TOTAL FIGURES 7
*Corresponding author. Tel.: +66 2218 7602; fax: +66 2218 7603; e-mail address:supot.h@chula.ac.th
1 of 25Tuesday , May 31, 2005Elsevier
 
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ABSTRACT
The severe acute respiratory syndrome - coronavirus (SARS-CoV), a new family of the coronavirus was finally proven to be the cause of SARS. The three-dimensionalstructure of the enzyme target is required in the development of diagnostic tests,antiviral therapies, and vaccines. Models of SARS-CoV proteinase in monomer anddimer forms were proposed. Although, the monomer form was assumed to be a targetfor Anti-SARS drug design, its appropriateness as a model has not yet been proven.The molecular dynamics simulations revealed significant discrepancy between themonomer and dimer models. The deviation of the electrostatic potential confirms theconclusion on the different roles of the two forms. The flexibility of the substrate- binding loop regions and the overall residue flexibility in each chain of the dimer form were discussed. Evidence show that the different conformations and interactions between SARS-CoV proteinase and substrate may be related to the N-terminalinteracting with the other chain when the dimer was formed.
 Keywords
:SARS; coronavirus; proteinase; MD simulation
2 of 25Tuesday , May 31, 2005Elsevier
 
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1. INTRODUCTION
The unprecedented technology in the post genomics era, particularly in molecular  biology and bioinformatics focused on the severe acute respiratory syndrome (SARS)outbreak is beginning to yield hints about how to fight the disease. Within 3 weeks of searching for the aetiological agent, scientists in several laboratories were able tosequence the novel sequences of the ~30,000-nucleotide RNA genomes of twoisolates of the SARS-CoV [1-2]. The genome showed all the feature characteristics of acoronavirus, but is significantly different from all previously known coronaviruses.Thus, the SARS-CoV represents a new coronavirus group. The genomes of theSARS-CoV Tor2 strain from Toronto [2] and the Urbani strain from Vietnam [1]differ by just eight nucleotides. The amino acid sequences of SARS-CoV isolatedfrom five patients in Singapore and those from Canada, the United States, and Chinahave been compared. The research teams from the four countries reported that overall,the virus is relatively stable compared to many other RNA viruses [3]. On May 13,2003 German researchers proposed a probable structure of one of the key proteinsinvolved in the virus's replication, based on the homology modeling technique usingthe available sequence alignment a development that could provide a possible drugtarget [4]. The predicted amino acid sequences of the viral proteinase enzyme, whichis part of the viral replicase polyprotein, and the spike (S) glycoproteins, the envelope(E) protein, the membrane (M) protein, the nucleocapsid (N), and the 3C like (3CL) proteinase of SARS-CoV suggests that they are structurally and functionallyhomologous to the proteins of known coronaviruses. The pair-wise amino acidsequence identity and similarity with their homologs is about 35 to 65% [5],respectively. The 3CL proteinase is supposed to be one of the potential targets for the
3 of 25Tuesday , May 31, 2005Elsevier

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