نتایج جستجو برای: cypa
تعداد نتایج: 264 فیلتر نتایج به سال:
We report here on the characterization of the novel immunosuppressant Sanglifehrin A (SFA). SFA is a representative of a class of macrolides produced by actinomycetes that bind to cyclophilin A (CypA), the binding protein of the fungal cyclic peptide cyclosporin A (CsA). SFA interacts with high affinity with the CsA binding side of CypA and inhibits its peptidyl-prolyl isomerase activity. The m...
Enzyme catalysis is central to almost all biochemical processes, speeding up rates of reactions to biological relevant timescales. Enzymes make use of a large ensemble of conformations in recognizing their substrates and stabilizing the transition states, due to the inherent dynamical nature of biomolecules. The exact role of these diverse enzyme conformations and the interplay between enzyme c...
33 Determining the interconverting conformations of dynamic proteins in atomic detail is a major challenge for 34 structural biology. Conformational heterogeneity in the active site of the dynamic enzyme cyclophilin A (CypA) 35 has been previously linked to its catalytic function, but the extent to which the different conformations of these 36 residues are correlated is unclear. Here we compare...
33 Determining the interconverting conformations of dynamic proteins in atomic detail is a major challenge for 34 structural biology. Conformational heterogeneity in the active site of the dynamic enzyme cyclophilin A (CypA) 35 has been previously linked to its catalytic function, but the extent to which the different conformations of these 36 residues are correlated is unclear. Here we compare...
New World monkeys of the genus Aotus synthesize a fusion protein (AoT5Cyp) containing tripartite motif-containing 5 (TRIM5) and cyclophilin A (CypA) that potently blocks HIV-1 infection. We attempted to generate a human HIV-1 inhibitor modeled after AoT5Cyp, by fusing human CypA to human TRIM5 (hT5Cyp). Of 13 constructs, 3 showed substantial HIV-1-inhibitory activity when expressed in human cel...
Skin cancer is the most common malignancy in organ transplant recipients, causing serious morbidity and mortality. Preventing and treating skin cancer in these individuals has been extraordinarily challenging. Following organ transplantation, cyclosporin A (CsA) has been used as an effective immunosuppressive to prevent rejection. Therefore immunosuppression has been widely assumed to be the ma...
HIV-1 replication is dependent on binding of the viral capsid to the host protein cyclophilin A (CypA). Interference with cyclophilin A binding, either by mutations in the HIV-1 capsid protein (CA) or by the drug cyclosporine A (CsA), inhibits HIV-1 replication in cell culture. Resistance to CsA is conferred by A92E or G94D substitutions in CA. The mutant viruses are also dependent on CsA for t...
Lentiviruses such as HIV-1 traverse nuclear pore complexes (NPC) and infect terminally differentiated non-dividing cells, but how they do this is unclear. The cytoplasmic NPC protein Nup358/RanBP2 was identified as an HIV-1 co-factor in previous studies. Here we report that HIV-1 capsid (CA) binds directly to the cyclophilin domain of Nup358/RanBP2. Fusion of the Nup358/RanBP2 cyclophilin (Cyp)...
DEB025/Debio 025 (Alisporivir) is a cyclophilin (Cyp)-binding molecule with potent anti-hepatitis C virus (HCV) activity both in vitro and in vivo. It is currently being evaluated in phase II clinical trials. DEB025 binds to CypA, a peptidyl-prolyl cis-trans isomerase which is a crucial cofactor for HCV replication. Here we report that it was very difficult to select resistant replicons (genoty...
Human immunodeficiency virus type 1 (HIV-1) normally enters cells by direct fusion with the plasma membrane. In this report, HIV-1 particles capable of infecting cells through an endocytic pathway are described. Chimeric viruses composed of the HIV-1 core and the envelope glycoprotein of vesicular stomatitis virus (VSV-G) were constructed and are herein termed HIV-1(VSV) pseudotypes. HIV-1(VSV)...
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