Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We isolated a novel gene encoding a protein highly homologous to human FK506-binding protein 12kDa (hFKBP-12) from a human fetal brain cDNA library and determined the full-length cDNA sequence. The cDNA clone contained the open reading frame of 324 nucleotides encoding 108 amino acid and revealed 76% identity in DNA sequence and 88% identity in predicted amino acid sequence with hFKBP-12. The DNA and amino-acid sequence of this gene, designated OTK4, also had homology with other FKBPs in species ranging from humans to prokaryotes. Recombinant protein, produced in E.coli transformed by a pGEX2T expression vector containing the OTK4 cDNA and purified, showed peptidyl-prolyl cis-trans isomerase activity like other FKBP proteins. An alternatively spliced form of the transcript found in the cDNA library contained a 45-bp insertion which included a stop codon. Although the biological function of the truncated version of OTK4 is unknown, both transcripts were ubiquitously expressed in human tissues examined by the reverse-transcriptase PCR (RT-PCR) method.
 ...
PMID:Molecular cloning and expression of a novel human gene that is highly homologous to human FK506-binding protein 12kDa (hFKBP-12) and characterization of two alternatively spliced transcripts. 751 96

Cyclophilins (Cyps) are proteins that are ubiquitously present with peptidyl-prolyl cis-trans isomerase activity and play an important role in de novo protein folding and in isomerization of native proteins in several cellular systems. There is growing evidence that indicates CypB is a positive modulator of the HCV RNA-dependent RNA polymerase in the replication complex. Early in vitro and animal data with selective Cyp inhibitors show a potent anti-HCV effect. This anti-HCV effect was confirmed in the first patient study with the selective Cyp inhibitor Debio-025. Preclinical data suggest that Cyp inhibitors may present a higher barrier to the selection of resistance than protease and polymerase inhibitors and that a combination of Cyp inhibitors with either of these drugs or interferon results in additive or synergistic anti-HCV activity. By interfering at the level of host-viral interaction, Cyp inhibition may open the way for a novel approach to anti-HCV treatment that could be complementary, not only to interferon-based treatment, but also to future treatments that directly target HCV replication enzymes such as protease and polymerase inhibitors.
 ...
PMID:Cyclophilin inhibitors in hepatitis C viral infection. 1771 21