scholarly journals The non-structural protein Nsp10 of mouse hepatitis virus binds zinc ions and nucleic acids

FEBS Letters ◽  
2006 ◽  
Vol 580 (17) ◽  
pp. 4143-4149 ◽  
Author(s):  
Nele Matthes ◽  
Jeroen R. Mesters ◽  
Bruno Coutard ◽  
Bruno Canard ◽  
Eric J. Snijder ◽  
...  
2002 ◽  
Vol 76 (10) ◽  
pp. 4987-4999 ◽  
Author(s):  
Lili Kuo ◽  
Paul S. Masters

ABSTRACT The coronavirus membrane (M) protein is the most abundant virion protein and the key component in viral assembly and morphogenesis. The M protein of mouse hepatitis virus (MHV) is an integral membrane protein with a short ectodomain, three transmembrane segments, and a large carboxy-terminal endodomain facing the interior of the viral envelope. The carboxy terminus of MHV M has previously been shown to be extremely sensitive to mutation, both in a virus-like particle expression system and in the intact virion. We have constructed a mutant, MΔ2, containing a two-amino-acid truncation of the M protein that was previously thought to be lethal. This mutant was isolated by means of targeted RNA recombination with a powerful host range-based selection allowed by the interspecies chimeric virus fMHV (MHV containing the ectodomain of the feline infectious peritonitis virus S protein). Analysis of multiple second-site revertants of the MΔ2 mutant has revealed changes in regions of both the M protein and the nucleocapsid (N) protein that can compensate for the loss of the last two residues of the M protein. Our data thus provide the first genetic evidence for a structural interaction between the carboxy termini of the M and N proteins of MHV. In addition, this work demonstrates the efficacy of targeted recombination with fMHV for the systematic genetic analysis of coronavirus structural protein interactions.


2002 ◽  
Vol 83 (2) ◽  
pp. 395-402 ◽  
Author(s):  
Walter Juergen Wurzer ◽  
Karola Obojes ◽  
Reinhard Vlasak

Group 2 coronaviruses are characterized within the order Nidovirales by a unique genome organization. A characteristic feature of group 2 coronaviruses is the presence of a gene encoding the haemagglutinin–esterase (HE) protein, which is absent in coronaviruses of groups 1 and 3. At least three coronavirus strains within group 2 expressed a structural protein with sialate-4-O-acetylesterase activity, distinguishing them from other members of group 2, which encode an enzyme specific for 5-N-acetyl-9-O-acetylneuraminic acid. The esterases of mouse hepatitis virus (MHV) strains S and JHM and puffinosis virus (PV) specifically hydrolysed 5-N-acetyl-4-O-acetylneuraminic acid (Neu4,5Ac2) as well as the synthetic substrates p-nitrophenyl acetate, 4-methylumbelliferyl acetate and fluorescein diacetate. The K m values of the MHV-like esterases for the latter substrates were two- to tenfold lower than those of the sialate-9-O-acetylesterases of influenza C viruses. Another unspecific esterase substrate, α-naphthyl acetate, was used for the in situ detection of the dimeric HE proteins in SDS–polyacrylamide gels. MHV-S, MHV-JHM and PV bound to horse serum glycoproteins containing Neu4,5Ac2. De-O-acetylation of the glycoproteins by alkaline treatment or incubation with the viral esterases resulted in a complete loss of recognition, indicating a specific interaction of MHV-like coronaviruses with Neu4,5Ac2. Combined with evidence for distinct phylogenetic lineages of group 2 coronaviruses, subdivision into subgroups 2a (MHV-like viruses) and 2b (bovine coronavirus-like viruses) is suggested.


PLoS ONE ◽  
2009 ◽  
Vol 4 (7) ◽  
pp. e6217 ◽  
Author(s):  
Xiaoling Xu ◽  
Zhiyong Lou ◽  
Yanlin Ma ◽  
Xuehui Chen ◽  
Zhangsheng Yang ◽  
...  

1988 ◽  
Author(s):  
Joan M. Cook-Mills ◽  
Hidayatulla G. Munshi ◽  
Robert L. Perlman ◽  
Donald A. Chambers

2019 ◽  
Vol 18 (32) ◽  
pp. 2774-2799 ◽  
Author(s):  
Krishnan Balasubramanian

We review various mathematical and computational techniques for drug discovery exemplifying some recent works pertinent to group theory of nested structures of relevance to phylogeny, topological, computational and combinatorial methods for drug discovery for multiple viral infections. We have reviewed techniques from topology, combinatorics, graph theory and knot theory that facilitate topological and mathematical characterizations of protein-protein interactions, molecular-target interactions, proteomics, genomics and statistical data reduction procedures for a large set of starting chemicals in drug discovery. We have provided an overview of group theoretical techniques pertinent to phylogeny, protein dynamics especially in intrinsically disordered proteins, DNA base permutations and related algorithms. We consider computational techniques derived from high level quantum chemical computations such as QM/MM ONIOM methods, quantum chemical optimization of geometries complexes, and molecular dynamics methods for providing insights into protein-drug interactions. We have considered complexes pertinent to Hepatitis Virus C non-structural protein 5B polymerase receptor binding of C5-Arylidebne rhodanines, complexes of synthetic potential vaccine molecules with dengue virus (DENV) and HIV-1 virus as examples of various simulation studies that exemplify the utility of computational tools. It is demonstrated that these combinatorial and computational techniques in conjunction with experiments can provide promising new insights into drug discovery. These techniques also demonstrate the need to consider a new multiple site or allosteric binding approach to drug discovery, as these studies reveal the existence of multiple binding sites.


1997 ◽  
Vol 46 (3) ◽  
pp. 211-218 ◽  
Author(s):  
Hodaka SUZUKI ◽  
Wijit KIATIPATTANASAKUL ◽  
Satoru KAJIKAWA ◽  
Shigeki TSUTSUI ◽  
Hiroyuki NAKAYAMA ◽  
...  

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