Rational Evolution of a Novel Type of Potent and Selective Proviral Integration Site in Moloney Murine Leukemia Virus Kinase 1 (PIM1) Inhibitor from a Screening-Hit Compound

2012 ◽  
Vol 55 (11) ◽  
pp. 5151-5164 ◽  
Author(s):  
Hirofumi Nakano ◽  
Nae Saito ◽  
Lorien Parker ◽  
Yukio Tada ◽  
Masanao Abe ◽  
...  
Keyword(s):  
Murine Leukemia Virus ◽  
Integration Site ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
Proviral Integration ◽  
Proviral Integration Site ◽  
Murine Leukemia

scholarly journals Proviral Integration Site for Moloney Murine Leukemia Virus (PIM) Kinases Promote Human T Helper 1 Cell Differentiation

2012 ◽  
Vol 288 (5) ◽  
pp. 3048-3058 ◽  
Author(s):  
Johanna Tahvanainen ◽  
Minna K. Kyläniemi ◽  
Kartiek Kanduri ◽  
Bhawna Gupta ◽  
Hanna Lähteenmäki ◽  
...  
Keyword(s):  
Murine Leukemia Virus ◽  
Integration Site ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
T Helper ◽  
T Helper 1 ◽  
Proviral Integration ◽  
Proviral Integration Site ◽  
Pim Kinases ◽  
Murine Leukemia

scholarly journals Insights into the Interaction Mechanisms of the Proviral Integration Site of Moloney Murine Leukemia Virus (Pim) Kinases with Pan-Pim Inhibitors PIM447 and AZD1208: A Molecular Dynamics Simulation and MM/GBSA Calculation Study

2019 ◽  
Vol 20 (21) ◽  
pp. 5410 ◽  
Author(s):  
Qingqing Chen ◽  
Yan Wang ◽  
Shanshan Shi ◽  
Kaihang Li ◽  
Ling Zhang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Murine Leukemia Virus ◽  
Integration Site ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
Proviral Integration ◽  
Interaction Mechanisms ◽  
Proviral Integration Site ◽  
Pim Kinases ◽  
Murine Leukemia

Based on the up-regulation of the proviral integration site of the Moloney murine leukemia virus (Pim) kinase family (Pim1, 2, and 3) observed in several types of leukemias and lymphomas, the development of pan-Pim inhibitors is an attractive therapeutic strategy. While only PIM447 and AZD1208 have entered the clinical stages. To elucidate the interaction mechanisms of three Pim kinases with PIM447 and AZD1208, six Pim/ligand systems were studied by homology modeling, molecular docking, molecular dynamics (MD) simulation and molecular mechanics/generalized Born surface area (MM/GBSA) binding free energy calculation. The residues of the top group (Leu44, Val52, Ala65, Lys67, and Leu120 in Pim1) dominated the pan-Pim inhibitors binding to Pim kinases. The residues of the bottom group (Gln127, Asp128, and Leu174 in Pim1) were crucial for Pims/PIM447 systems, while the contributions of these residues were decreased sharply for Pims/AZD1208 systems. It is likely that the more potent pan-Pim inhibitors should be bound strongly to the top and bottom groups. The residues of the left, right and loop groups were located in the loop regions of the binding pocket, however, the flexibility of these regions triggered the protein interacting with diverse pan-Pim inhibitors efficiently. We hope this work can provide valuable information for the design of novel pan-Pim inhibitors in the future.

scholarly journals Fre2, a proviral integration site of Friend murine leukemia virus that is closely linked to Fv2

Leukemia ◽  
1997 ◽  
Vol 11 (5) ◽  
pp. 619-623 ◽  
Author(s):  
RW Friedrich ◽  
M Veit ◽  
D Eisel ◽  
U Friedrich ◽  
M Pass ◽  
...  
Keyword(s):  
Murine Leukemia Virus ◽  
Integration Site ◽  
Leukemia Virus ◽  
Proviral Integration ◽  
Proviral Integration Site ◽  
Murine Leukemia

scholarly journals A Chimeric Ty3/Moloney Murine Leukemia Virus Integrase Protein Is Active In Vivo

1998 ◽  
Vol 72 (5) ◽  
pp. 4297-4307 ◽  
Author(s):  
Sandra L. Dildine ◽  
James Respess ◽  
Doug Jolly ◽  
Suzanne B. Sandmeyer
Keyword(s):  
Cell Line ◽  
Murine Leukemia Virus ◽  
Genomic Dna ◽  
Integration Site ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
Packaging Cell Line ◽  
Terminal Domain ◽  
Murine Leukemia

ABSTRACT This report describes the results of experiments to determine whether chimeras between a retrovirus and portions of Ty3 are active in vivo. A chimera between Ty3 and a Neor-marked Moloney murine leukemia virus (M-MuLV) was constructed. The C-terminal domain of M-MuLV integrase (IN) was replaced with the C-terminal domain of Ty3 IN. The chimeric retroviruses were expressed from an amphotrophic envelope packaging cell line. The virus generated was used to infect the human fibrosarcoma cell line HT1080, and cells in which integration had occurred were selected by G418 resistance. Three independently integrated viruses were rescued. In each case, the C-terminal Ty3 IN sequences were maintained and short direct repeats of the genomic DNA flanked the integration site. Sequence analysis of the genomic DNA flanking the insertion did not identify a tRNA gene; therefore, these integration events did not have Ty3 position specificity. This study showed that IN sequences from the yeast retrovirus-like element Ty3 can substitute for M-MuLV IN sequences in the C-terminal domain and contribute to IN function in vivo. It is also one of the first in vivo demonstrations of activity of a retrovirus encoding an integrase chimera. Studies of chimeras between IN species with distinctive integration patterns should complement previous work by expanding our understanding of the roles of nonconserved domains.

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