comparison of newly assembled full length hiv-1 integrase with prototype foamy virus integrase: structure-function prospective
نویسندگان
چکیده
background drug design against human immunodeficiency virus type 1 (hiv-1) integrase through its mechanistic study is of great interest in the area in biological research. the main obstacle in this area is the absence of the full-length crystal structure for hiv-1 integrase to be used as a model. a complete structure, similar to hiv-1 of a prototype foamy virus integrase in complex with dna, including all conservative residues, is available and has been extensively used in recent investigations. conclusions based on our findings, we can conclude that hiv-1 integrase is vastly different from the prototype foamy virus integrase and does not resemble it, and the modeling output of the prototype foamy virus simulations could not be simply generalized to hiv-1 integrase. therefore, our hiv-1 model seems to be more representative and more useful for future research. objectives the aim of this study was to determine whether the above model is precisely representative of hiv-1 integrase. this would critically determine the success of any designed drug using the model in deactivation of integrase and aids treatment. materials and methods primarily, a new structure for hiv-1 was constructed, using a crystal structure of prototype foamy virus as the starting structure. the constructed structure of hiv-1 integrase was simultaneously simulated with a prototype foamy virus integrase on a separate occasion. results our results indicate that the hiv-1 system behaves differently from the prototype foamy virus in terms of folding, hydration, hydrophobicity of binding site and stability.
منابع مشابه
Comparison of Newly Assembled Full Length HIV-1 Integrase With Prototype Foamy Virus Integrase: Structure-Function Prospective
BACKGROUND Drug design against human immunodeficiency virus type 1 (HIV-1) integrase through its mechanistic study is of great interest in the area in biological research. The main obstacle in this area is the absence of the full-length crystal structure for HIV-1 integrase to be used as a model. A complete structure, similar to HIV-1 of a prototype foamy virus integrase in complex with DNA, in...
متن کاملMinimal size of prototype foamy virus integrase for nuclear localization.
We have reported previously that the prototype foamy virus (PFV) integrase (IN) has a strong nuclear localization signal (NLS) in its C-terminal domain, in particular in a region of aa 306-334 including highly karyophilic arginines or lysines at positions 308, 313, 318, 324, and 329. In this study, we used various mutants of the C-terminal domain to further analyze its karyophilic determinants....
متن کاملAn active foamy virus integrase is required for virus replication.
Foamy viruses (FVs) make use of a replication strategy which is unique among retroviruses and shows analogies to hepadnaviruses. The presence of an integrase (IN) and obligate provirus integration distinguish retroviruses from hepadnaviruses. To clarify whether a functional IN is required for FV replication, a mutant in the highly conserved DD35E motif of the active centre was analysed. This mu...
متن کاملStructure of the catalytic domain of avian sarcoma virus integrase with a bound HIV-1 integrase-targeted inhibitor.
The x-ray structures of an inhibitor complex of the catalytic core domain of avian sarcoma virus integrase (ASV IN) were solved at 1.9- to 2.0-A resolution at two pH values, with and without Mn2+ cations. This inhibitor (Y-3), originally identified in a screen for inhibitors of the catalytic activity of HIV type 1 integrase (HIV-1 IN), was found in the present study to be active against ASV IN ...
متن کاملFunctional and structural characterization of the integrase from the prototype foamy virus
Establishment of the stable provirus is an essential step in retroviral replication, orchestrated by integrase (IN), a virus-derived enzyme. Until now, available structural information was limited to the INs of human immunodeficiency virus type 1 (HIV-1), avian sarcoma virus (ASV) and their close orthologs from the Lentivirus and Alpharetrovirus genera. Here, we characterized the in vitro activ...
متن کاملRemoval of nuclease contamination during purification of recombinant prototype foamy virus integrase.
Retroviral infection requires integration of the viral genome into the host genome. Recombinant integrase proteins may be purified following bacterial expression. A bulk biochemical assay of integrase function relies on the conversion of supercoiled plasmids to linear or relaxed circles. Single molecule molecular tweezer assays of integrase also evaluate the conversion of supercoiled DNA to nic...
متن کاملمنابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
jundishapur journal of microbiologyجلد ۹، شماره ۵، صفحات ۰-۰
میزبانی شده توسط پلتفرم ابری doprax.com
copyright © 2015-2023