Stabilization of Human Serum Albumin by the Binding of Phycocyanobilin, a Bioactive Chromophore of Blue-Green Alga Spirulina: Molecular Dynamics and Experimental Study
2016
Аутори
Radibratović, MilicaMinić, Simeon L.
Stanić-Vučinić, Dragana
Nikolić, Milan
Milčić, Miloš K.
Ćirković-Veličković, Tanja
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Phycocyanobilin (PCB) binds with high affinity (2.2 x 10 6 M-1 at 25 degrees C) to human serum albumin (HSA) at sites located in IB and IIA subdomains. The aim of this study was to examine effects of PCB binding on protein conformation and stability. Using 300 ns molecular dynamics (MD) simulations, UV-VIS spectrophotometry, CD, FT-IR, spectrofluorimetry, thermal denaturation and susceptibility to trypsin digestion, we studied the effects of PCB binding on the stability and rigidity of HSA, as well as the conformational changes in PCB itself upon binding to the protein. MD simulation results demonstrated that HSA with PCB bound at any of the two sites showed greater rigidity and lower overall and individual domain flexibility compared to free HSA. Experimental data demonstrated an increase in the a-helical content of the protein and thermal and proteolytic stability upon ligand binding. PCB bound to HSA undergoes a conformational change to a more elongated conformation in the binding p...ockets of HSA. PCB binding to HSA stabilizes the structure of this flexible transport protein, making it more thermostable and resistant to proteolysis. The results from this work explain at molecular level, conformational changes and stabilization of HSA structure upon ligand binding. The resultant increased thermal and proteolytic stability of HSA may provide greater longevity to HSA in plasma.
Извор:
PLoS One / Public Library of Science, 2016, 11, 12Издавач:
- Public Library Science, San Francisco
Финансирање / пројекти:
- Молекуларне особине и модификације неких респираторних и нутритивних алергена (RS-MESTD-Basic Research (BR or ON)-172024)
- Reinforcement of the Faculty of Chemistry, University of Belgrade, towards becoming a Center of Excellence in the region of WB for Molecular Biotechnology and Food research (EU-FP7-256716)
Напомена:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3614
DOI: 10.1371/journal.pone.0167973
ISSN: 1932-6203
PubMed: 27959940
WoS: 000392753900028
Scopus: 2-s2.0-85006056883
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Radibratović, Milica AU - Minić, Simeon L. AU - Stanić-Vučinić, Dragana AU - Nikolić, Milan AU - Milčić, Miloš K. AU - Ćirković-Veličković, Tanja PY - 2016 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1948 AB - Phycocyanobilin (PCB) binds with high affinity (2.2 x 10 6 M-1 at 25 degrees C) to human serum albumin (HSA) at sites located in IB and IIA subdomains. The aim of this study was to examine effects of PCB binding on protein conformation and stability. Using 300 ns molecular dynamics (MD) simulations, UV-VIS spectrophotometry, CD, FT-IR, spectrofluorimetry, thermal denaturation and susceptibility to trypsin digestion, we studied the effects of PCB binding on the stability and rigidity of HSA, as well as the conformational changes in PCB itself upon binding to the protein. MD simulation results demonstrated that HSA with PCB bound at any of the two sites showed greater rigidity and lower overall and individual domain flexibility compared to free HSA. Experimental data demonstrated an increase in the a-helical content of the protein and thermal and proteolytic stability upon ligand binding. PCB bound to HSA undergoes a conformational change to a more elongated conformation in the binding pockets of HSA. PCB binding to HSA stabilizes the structure of this flexible transport protein, making it more thermostable and resistant to proteolysis. The results from this work explain at molecular level, conformational changes and stabilization of HSA structure upon ligand binding. The resultant increased thermal and proteolytic stability of HSA may provide greater longevity to HSA in plasma. PB - Public Library Science, San Francisco T2 - PLoS One / Public Library of Science T1 - Stabilization of Human Serum Albumin by the Binding of Phycocyanobilin, a Bioactive Chromophore of Blue-Green Alga Spirulina: Molecular Dynamics and Experimental Study VL - 11 IS - 12 DO - 10.1371/journal.pone.0167973 ER -
@article{ author = "Radibratović, Milica and Minić, Simeon L. and Stanić-Vučinić, Dragana and Nikolić, Milan and Milčić, Miloš K. and Ćirković-Veličković, Tanja", year = "2016", abstract = "Phycocyanobilin (PCB) binds with high affinity (2.2 x 10 6 M-1 at 25 degrees C) to human serum albumin (HSA) at sites located in IB and IIA subdomains. The aim of this study was to examine effects of PCB binding on protein conformation and stability. Using 300 ns molecular dynamics (MD) simulations, UV-VIS spectrophotometry, CD, FT-IR, spectrofluorimetry, thermal denaturation and susceptibility to trypsin digestion, we studied the effects of PCB binding on the stability and rigidity of HSA, as well as the conformational changes in PCB itself upon binding to the protein. MD simulation results demonstrated that HSA with PCB bound at any of the two sites showed greater rigidity and lower overall and individual domain flexibility compared to free HSA. Experimental data demonstrated an increase in the a-helical content of the protein and thermal and proteolytic stability upon ligand binding. PCB bound to HSA undergoes a conformational change to a more elongated conformation in the binding pockets of HSA. PCB binding to HSA stabilizes the structure of this flexible transport protein, making it more thermostable and resistant to proteolysis. The results from this work explain at molecular level, conformational changes and stabilization of HSA structure upon ligand binding. The resultant increased thermal and proteolytic stability of HSA may provide greater longevity to HSA in plasma.", publisher = "Public Library Science, San Francisco", journal = "PLoS One / Public Library of Science", title = "Stabilization of Human Serum Albumin by the Binding of Phycocyanobilin, a Bioactive Chromophore of Blue-Green Alga Spirulina: Molecular Dynamics and Experimental Study", volume = "11", number = "12", doi = "10.1371/journal.pone.0167973" }
Radibratović, M., Minić, S. L., Stanić-Vučinić, D., Nikolić, M., Milčić, M. K.,& Ćirković-Veličković, T.. (2016). Stabilization of Human Serum Albumin by the Binding of Phycocyanobilin, a Bioactive Chromophore of Blue-Green Alga Spirulina: Molecular Dynamics and Experimental Study. in PLoS One / Public Library of Science Public Library Science, San Francisco., 11(12). https://doi.org/10.1371/journal.pone.0167973
Radibratović M, Minić SL, Stanić-Vučinić D, Nikolić M, Milčić MK, Ćirković-Veličković T. Stabilization of Human Serum Albumin by the Binding of Phycocyanobilin, a Bioactive Chromophore of Blue-Green Alga Spirulina: Molecular Dynamics and Experimental Study. in PLoS One / Public Library of Science. 2016;11(12). doi:10.1371/journal.pone.0167973 .
Radibratović, Milica, Minić, Simeon L., Stanić-Vučinić, Dragana, Nikolić, Milan, Milčić, Miloš K., Ćirković-Veličković, Tanja, "Stabilization of Human Serum Albumin by the Binding of Phycocyanobilin, a Bioactive Chromophore of Blue-Green Alga Spirulina: Molecular Dynamics and Experimental Study" in PLoS One / Public Library of Science, 11, no. 12 (2016), https://doi.org/10.1371/journal.pone.0167973 . .