Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recombinant rabies virus phosphoprotein fusion product (GST-P) was used to generate a series of monoclonal antibodies (MAbs) with anti-P reactivity. Competitive binding assays classified 27 of these MAbs into four groups (I to IV), and 24 of them were deemed to recognize linear epitopes, as judged by their reaction in immunoblots. The linear epitope recognized in each case was mapped by using two series of N- and C-terminally deleted recombinant phosphoproteins. Assessment of the reactivities of representative MAbs to a variety of lyssavirus isolates by an indirect fluorescent antibody test indicated that group I MAbs, which recognized a highly conserved N-terminal epitope, were broadly cross-reactive with all lyssaviruses assayed, while group III MAbs, which reacted with a site overlapping that of group I MAbs, exhibited variable reactivities and group IV MAbs reacted with most isolates of genotypes 1, 6, and 7 only. In contrast, group II MAbs, which recognized an epitope located within a highly divergent central portion of the protein, were exquisitely strain specific. These anti-P MAbs are potentially useful tools for lyssavirus identification and discrimination.
...
PMID:A panel of monoclonal antibodies targeting the rabies virus phosphoprotein identifies a highly variable epitope of value for sensitive strain discrimination. 1074 14

To investigate the immune response to anti-rabies vaccination in the principal recipient (the domestic dog), four truncated fragments of the rabies virus glycoprotein were expressed as glutathione S-transferase fusion proteins. Immune sera from vaccinated rabbits and dogs were then used to probe for reactivity with these expressed proteins. In two rabbits and four dogs tested, the dominant antibody response to non-conformational antigenic sites appeared to be directed to a region of the glycoprotein between amino acids 222 and 332. The N-terminal fragment of the glycoprotein was also significantly antigenic. Further studies to assess whether the antibody response to the internal domain could neutralize the rabies Challenge Virus Standard (CVS) strain, using antibody depletion, suggested that this fraction did contribute to the ability of post-vaccination sera to neutralize and therefore protect against infection.
...
PMID:Canine vaccine recipients recognize an immunodominant region of the rabies virus glycoprotein. 1238 1

Rabies virus glycoprotein (G) is a trimeric type I transmembrane glycoprotein that mediates both receptor recognition and low pH-induced membrane fusion. Electron microscopy has indicated that the ectodomain of protein G is made of a globular head and a stem. In order to characterize the putative stem region at the molecular level, we designed two peptides, P(S) and P(L), which were produced as GST fusion proteins in bacteria. Peptide P(S) extends from amino acid (aa) 374 to aa 428 whereas peptide P(L) extends from aa 368 down to the end of the ectodomain of G (aa 439). Their secondary and quaternary structures have been studied with spectroscopic and biophysical methods. We show that these isolated peptides are monomeric and poorly structured in aqueous solution. However, circular dichroism (CD) in presence of 2,2,2-trifluoroethanol and NMR data indicate that this region may adopt a alpha-helical conformation in the complete glycoprotein.
...
PMID:Spectroscopic characterization of two peptides derived from the stem of rabies virus glycoprotein. 1278 63

Rabies virus P protein is a cofactor of RNA polymerase. We investigated other potential roles of P (CVS strain) by searching for cellular partners using two-hybrid screening. We isolated a cDNA encoding the signal transducer and activator of transcription 1 (STAT1) that is a critical component of interferon type I (IFN-alpha/beta) and type II (IFN-gamma) signaling. We confirmed this interaction by glutathione S-transferase-pull-down assay. Deletion mutant analysis indicated that the carboxy-terminal part of P interacted with a region containing the DNA-binding domain and the coiled-coil domain of STAT1. The expression of P protein inhibits IFN-alpha- and IFN-gamma-induced transcriptional responses, thus impairing the IFN-induced antiviral state. Mechanistic studies indicate that P protein does not induce STAT1 degradation and does not interfere with STAT1 phosphorylation but prevents IFN-induced STAT1 nuclear accumulation. These results indicate that rabies P protein overcomes the antiviral response of the infected cells.
...
PMID:Rabies virus P protein interacts with STAT1 and inhibits interferon signal transduction pathways. 1625 75

Rabies virus (RABV), the causative agent of rabies, is highly neurovirulent for warm-blooded animals with a mortality rate of up to 100%. The RABV matrix protein (M) is required for virus particle assembly and budding. However, little is known about antigenic differences in the M protein. In this study, five monoclonal antibodies (mAbs), designated 3B9, 4A1, 2B11, 2C1, and 4B11, against the RABV M protein were generated using a recombinant M protein. All five mAbs reacted with the CVS-11 strain but showed no reactivity against the HEP-Flury strain in indirect immunofluorescence and western blotting. The epitope targeted by these mAbs was further identified by peptide scanning using GST-fused peptides. The ²⁵PPYDDD³⁰ peptide was defined as the minimal linear epitope. Alignment of amino acid sequences and phylogenetic analysis of different RABV strains indicated that the variable epitope ²⁵PPDGDD³⁰ is only present in the HEP-Flury and variant Flury strains of clade III, while the other strains resembling ERA and SRVA9 within the clade had another variable epitope, ²⁵PLDDDD³⁰. A Y27D mutation within the epitope was found among the rest of the RABV strains distributed in different clades. However, a single D28G mutation eliminated the reactivity of these five mAbs. In addition, the mAbs were able to recognize wildtype RABV strain in indirect immunofluorescence and western blotting and detect RABV-infected brain tissue using immunohistochemistry. The newly established mAbs and identified epitope may facilitate future investigations in the structure and function of the M protein and the development of diagnostic methods for the detection of different RABV strains worldwide. Most importantly, the epitope recognized by the mAbs against M protein might serve as a novel target for the development of a vaccine targeting RABV virulent strains.
...
PMID:Generation of Monoclonal Antibodies against Variable Epitopes of the M Protein of Rabies Virus. 3101 7

---