TY  - JOUR
AU  - Tintori, Cristina
AU  - Veljković, Nevena V.
AU  - Veljković, Veljko
AU  - Botta, Maurizio
PY  - 2010
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4144
AB  - A crystal structure of the integrase binding domain (IBD) of the lens epithelium-derived growth factor (LEDGF/p75) in complex with the dimer of the HIV-1 integrase (IN) catalytic core domain (CCD) provides useful information that might help in the understanding of essential protein-protein contacts in HIV-1. However, mutagenic studies indicated that interactions between the full-length proteins were more extensive than the contacts observed in the co-crystal structure of the isolated domains. On the other hand, the biochemical characterization of the interaction between full-length IN and LEDGF/p75 has recently proved that LEDGF/p75 promotes IN tetramerization with two LEDGF/p75 IBD molecules bound to the IN tetramer. This experimental evidence suggests that to obtain a complete structural description of the interactions between the two proteins, the full-length tetrameric structure of IN should be considered. Our aim was to obtain a detailed picture of HIV-1 IN interactions with cellular co-factors that was of general interest, particularly for the development of small molecule IN inhibitors, which mimic the IBD of LEDGF/p75. To this end, we performed bioinformatics analyses to identify protein sequence domains involved in long-range recognition. Subsequently, we applied molecular dynamics techniques to investigate the detailed interactions between the complete tetrameric form of IN and two molecules of the IBD of LEDGF/p75. Our dynamic picture is in agreement with experimental data and, thereby, provides new details of the IN-LEDGF/p75 interaction.
T2  - Proteins: Structure Function and Bioinformatics
T1  - Computational studies of the interaction between the HIV-1 integrase tetramer and the cofactor LEDGF/p75: Insights from molecular dynamics simulations and the informational spectrum method
VL  - 78
IS  - 16
SP  - 3396
EP  - 3408
DO  - 10.1002/prot.22847
ER  - 

@article{
author = "Tintori, Cristina and Veljković, Nevena V. and Veljković, Veljko and Botta, Maurizio",
year = "2010",
abstract = "A crystal structure of the integrase binding domain (IBD) of the lens epithelium-derived growth factor (LEDGF/p75) in complex with the dimer of the HIV-1 integrase (IN) catalytic core domain (CCD) provides useful information that might help in the understanding of essential protein-protein contacts in HIV-1. However, mutagenic studies indicated that interactions between the full-length proteins were more extensive than the contacts observed in the co-crystal structure of the isolated domains. On the other hand, the biochemical characterization of the interaction between full-length IN and LEDGF/p75 has recently proved that LEDGF/p75 promotes IN tetramerization with two LEDGF/p75 IBD molecules bound to the IN tetramer. This experimental evidence suggests that to obtain a complete structural description of the interactions between the two proteins, the full-length tetrameric structure of IN should be considered. Our aim was to obtain a detailed picture of HIV-1 IN interactions with cellular co-factors that was of general interest, particularly for the development of small molecule IN inhibitors, which mimic the IBD of LEDGF/p75. To this end, we performed bioinformatics analyses to identify protein sequence domains involved in long-range recognition. Subsequently, we applied molecular dynamics techniques to investigate the detailed interactions between the complete tetrameric form of IN and two molecules of the IBD of LEDGF/p75. Our dynamic picture is in agreement with experimental data and, thereby, provides new details of the IN-LEDGF/p75 interaction.",
journal = "Proteins: Structure Function and Bioinformatics",
title = "Computational studies of the interaction between the HIV-1 integrase tetramer and the cofactor LEDGF/p75: Insights from molecular dynamics simulations and the informational spectrum method",
volume = "78",
number = "16",
pages = "3396-3408",
doi = "10.1002/prot.22847"
}

Tintori, C., Veljković, N. V., Veljković, V.,& Botta, M.. (2010). Computational studies of the interaction between the HIV-1 integrase tetramer and the cofactor LEDGF/p75: Insights from molecular dynamics simulations and the informational spectrum method. in Proteins: Structure Function and Bioinformatics, 78(16), 3396-3408.
https://doi.org/10.1002/prot.22847

Tintori C, Veljković NV, Veljković V, Botta M. Computational studies of the interaction between the HIV-1 integrase tetramer and the cofactor LEDGF/p75: Insights from molecular dynamics simulations and the informational spectrum method. in Proteins: Structure Function and Bioinformatics. 2010;78(16):3396-3408.
doi:10.1002/prot.22847 .

Tintori, Cristina, Veljković, Nevena V., Veljković, Veljko, Botta, Maurizio, "Computational studies of the interaction between the HIV-1 integrase tetramer and the cofactor LEDGF/p75: Insights from molecular dynamics simulations and the informational spectrum method" in Proteins: Structure Function and Bioinformatics, 78, no. 16 (2010):3396-3408,
https://doi.org/10.1002/prot.22847 . .