Characterisation of the binding of dihydro-alpha-lipoic acid to fibrinogen and the effects on fibrinogen oxidation and fibrin formation
Апстракт
A reduced form of the alpha-lipoic acid, dihydro-alpha-lipoic acid (DHLA) is a potent, naturally occurring antioxidant which can be consumed as food constituent or as supplement at doses up to 600 mg/day. DHLA has inhibitory effect on coagulation as it can reduce concentrations of some coagulation factors. In this study, a direct interaction between DHLA and fibrinogen, the main protein in coagulation, is described. Binding constant for DHLA/fibrinogen complex is of moderate strength (104) and interaction probably occurs in D regions of fibrinogen, as shown by docking simulations. Fibrinogen stability remains the same with only marginal structural changes in its secondary structure favouring more ordered molecular organisation upon DHLA binding. Fibrinogen with bound DHLA forms fibrin with thicker fibers, as measured by coagulation assay and is protected from oxidation to certain extent. Obtained results support beneficial effects of DHLA on fibrinogen and consequently on coagulation p...rocess, suggesting that DHLA supplementation may be indicated for persons with an increased risk of developing thrombotic complications, particularly those whose fibrin is characterised by increased oxidative modification and formation of thinner and less porous fibers. Also, DHLA in complex with fibrinogen can be located at site of injury where it may exert antioxidant effects.
Кључне речи:
Protein interaction / Molecular modelling / Protein functionИзвор:
International Journal of Biological Macromolecules, 2020, 147, 319-325Издавач:
- Elsevier
Финансирање / пројекти:
- Структурне карактеристике везујућих протеина и рецептора за инсулину сличне факторе раста (IGF), њихове интеракције са другим физиолошким молекулима и промене код поремећаја метаболизма (RS-MESTD-Basic Research (BR or ON)-173042)
Напомена:
- This is the peer-reviewed version of the article: International Journal of Biological Macromolecules, 2020, 147, 319-325, doi: https://dx.doi.org/10.1016/j.ijbiomac.2020.01.098
- The published version: http://cer.ihtm.bg.ac.rs/handle/123456789/3378
DOI: 10.1016/j.ijbiomac.2020.01.098
ISSN: 0141-8130
WoS: 000525864700036
Scopus: 2-s2.0-85077757227
Институција/група
IHTMTY - JOUR AU - Gligorijević, Nikola AU - Šukalović, Vladimir AU - Penezić, Ana AU - Nedić, Olgica PY - 2020 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/3385 AB - A reduced form of the alpha-lipoic acid, dihydro-alpha-lipoic acid (DHLA) is a potent, naturally occurring antioxidant which can be consumed as food constituent or as supplement at doses up to 600 mg/day. DHLA has inhibitory effect on coagulation as it can reduce concentrations of some coagulation factors. In this study, a direct interaction between DHLA and fibrinogen, the main protein in coagulation, is described. Binding constant for DHLA/fibrinogen complex is of moderate strength (104) and interaction probably occurs in D regions of fibrinogen, as shown by docking simulations. Fibrinogen stability remains the same with only marginal structural changes in its secondary structure favouring more ordered molecular organisation upon DHLA binding. Fibrinogen with bound DHLA forms fibrin with thicker fibers, as measured by coagulation assay and is protected from oxidation to certain extent. Obtained results support beneficial effects of DHLA on fibrinogen and consequently on coagulation process, suggesting that DHLA supplementation may be indicated for persons with an increased risk of developing thrombotic complications, particularly those whose fibrin is characterised by increased oxidative modification and formation of thinner and less porous fibers. Also, DHLA in complex with fibrinogen can be located at site of injury where it may exert antioxidant effects. PB - Elsevier T2 - International Journal of Biological Macromolecules T1 - Characterisation of the binding of dihydro-alpha-lipoic acid to fibrinogen and the effects on fibrinogen oxidation and fibrin formation VL - 147 SP - 319 EP - 325 DO - 10.1016/j.ijbiomac.2020.01.098 ER -
@article{ author = "Gligorijević, Nikola and Šukalović, Vladimir and Penezić, Ana and Nedić, Olgica", year = "2020", abstract = "A reduced form of the alpha-lipoic acid, dihydro-alpha-lipoic acid (DHLA) is a potent, naturally occurring antioxidant which can be consumed as food constituent or as supplement at doses up to 600 mg/day. DHLA has inhibitory effect on coagulation as it can reduce concentrations of some coagulation factors. In this study, a direct interaction between DHLA and fibrinogen, the main protein in coagulation, is described. Binding constant for DHLA/fibrinogen complex is of moderate strength (104) and interaction probably occurs in D regions of fibrinogen, as shown by docking simulations. Fibrinogen stability remains the same with only marginal structural changes in its secondary structure favouring more ordered molecular organisation upon DHLA binding. Fibrinogen with bound DHLA forms fibrin with thicker fibers, as measured by coagulation assay and is protected from oxidation to certain extent. Obtained results support beneficial effects of DHLA on fibrinogen and consequently on coagulation process, suggesting that DHLA supplementation may be indicated for persons with an increased risk of developing thrombotic complications, particularly those whose fibrin is characterised by increased oxidative modification and formation of thinner and less porous fibers. Also, DHLA in complex with fibrinogen can be located at site of injury where it may exert antioxidant effects.", publisher = "Elsevier", journal = "International Journal of Biological Macromolecules", title = "Characterisation of the binding of dihydro-alpha-lipoic acid to fibrinogen and the effects on fibrinogen oxidation and fibrin formation", volume = "147", pages = "319-325", doi = "10.1016/j.ijbiomac.2020.01.098" }
Gligorijević, N., Šukalović, V., Penezić, A.,& Nedić, O.. (2020). Characterisation of the binding of dihydro-alpha-lipoic acid to fibrinogen and the effects on fibrinogen oxidation and fibrin formation. in International Journal of Biological Macromolecules Elsevier., 147, 319-325. https://doi.org/10.1016/j.ijbiomac.2020.01.098
Gligorijević N, Šukalović V, Penezić A, Nedić O. Characterisation of the binding of dihydro-alpha-lipoic acid to fibrinogen and the effects on fibrinogen oxidation and fibrin formation. in International Journal of Biological Macromolecules. 2020;147:319-325. doi:10.1016/j.ijbiomac.2020.01.098 .
Gligorijević, Nikola, Šukalović, Vladimir, Penezić, Ana, Nedić, Olgica, "Characterisation of the binding of dihydro-alpha-lipoic acid to fibrinogen and the effects on fibrinogen oxidation and fibrin formation" in International Journal of Biological Macromolecules, 147 (2020):319-325, https://doi.org/10.1016/j.ijbiomac.2020.01.098 . .