Compartment:
endoplasmic reticulum membrane,
cytosol,
integral component of cytoplasmic side of endoplasmic reticulum membrane
In mammals, polyprenol pyrophosphate (pPPP) requires dephosphorylation to polyprenol (pPNOL), which can then be reduced. Although pPPP phosphatase activity has been reported (Wolf et al. 1991), no pPPP phosphatase enzyme has yet been identified (Schenk et al. 2001).
N-acetylglucosaminyltransferase (GnT)-IV catalyzes the addition of GlcNAc beta,1,4 on the GlcNAc beta1,2 Man,alpha1,3 arm of both complex and hybrid N-glycans (Oguri S et al, 2006). Two human GnT-IV isozymes have been characterized (MGAT4A, MGAT4B) , plus a putative MGAT4C on chromosome 2 (Furukawa T et al, 1999). Aberrant expression of MGAT4A or MGAT4B is associated with pancreatic cancer (Ide Y et al, 2006; Kudo T et al , 2007)
SMUG1 is a single-strand selective monofunctional uracil DNA glycosylase that cleaves uracil from the sugar phosphate backbone of DNA. SMUG1 has the highest preference for uracil in single strand DNA, followed by A:U and then G:U pairs in double strand DNA (Haushalter et al. 1999, Masaoka et al. 2003).
SMUG1, a single-strand selective monofunctional uracil DNA glycosylase, recognizes and binds uracil residues in the DNA. SMUG1 shows a preference for single-strand DNA, although it also recognizes A:U and G:U pairs in double-strand DNA (Haushalter et al. 1999, Masaoka et al. 2003).
Anterograde trains travel along the axoneme of the cilium at an estimated rate of 2 micrometers per second in an ATP- and kinesin-2-dependent fashion (reviewed in Cole and Snell, 2009). Although the particulars of IFT train-cargo interactions have not been fully elaborated, recent studies in C. reinhardtii and human cells have shown that the IFT B components IFT74 and IFT81 have tubulin-binding sites, while IFT46 is required for the ciliary transport of the outer dynein arm, and more recently, TTC26 has been shown to be required for the transport of motility-related proteins into the flagella (Bhogaraju et al, 2013; Ahmed et al, 2008; Hou et al, 2007; Ishikawa et al, 2014; reviewed in Bhogarju et al, 2014).
Antiretroviral (ARV) therapy, comprising a backbone of two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus another ARV, has helped extend life expectancy in people living with HIV (Orkin et al. 2018). NRTIs work by inhibiting HIV reverse transcriptase (RT), preventing transcription of HIV RNA to DNA. Emtricitabine, a cytidine analogue (Feng et al. 2009, Al-Majed et al. 2020) and tenofovir, an acyclic nucleotide diester analogue of adenosine monophosphate (McConville et al. 2015, Ray et al. 2016) are compounds which inhibit RT causing chain termination and inhibition of viral protein synthesis.
Antiretroviral (ARV) therapy, comprising a backbone of two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus another ARV, has helped extend life expectancy in people living with HIV (Orkin et al. 2018).
Lopinavir is an antiretroviral protease inhibitor used in combination with other antiretrovirals in the treatment of HIV-1 infection. Like many other protease inhibitors, lopinavir is a peptidomimetic molecule; it contains a hydroxyethylene scaffold that mimics the peptide linkage typically targeted by the HIV-1 protease enzyme but which itself cannot be cleaved, thus preventing the acivity of the HIV-1 protease (Reddy et al. 2007). Another HIV protease inhibitor, darunavir, prevents HIV replication through binding to the enzyme, stopping the dimerization and the catalytic activity of HIV-1 protease (De Meyer et al. 2005). In particular, it inhibits the cleavage of HIV encoded Gag-Pol proteins in cells that have been infected with the virus, halting the formation of mature virus particles, which spread the infection (Davis et al. 2012).
Lopinavir in combination with other drugs is currently being investigated for patients with COVID-19 (many clinical trials, example registration nos. ChiCTR2000029603, ChiCTR2000029539, NCT04255017, NCT04261270) (Harrison 2020, Cao et al. 2020, Deng et al. 2020, Martinez 2020).