Structural Determinants Underlying the Interplay Between Fatty Acid Binding and S-Nitrosylation of Human Serum Albumin
4 affiliations
- 1Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Pr. Torez 44, 194223 St. Petersburg, Russia
- 2St. Petersburg State University, 7/9 Universitetskaya Nab., 199034 St. Petersburg, Russia
- 3Leicester School of Allied Health Sciences, De Montfort University, The Gateway, Leicester LE1 9BH, UK
- 4Department of Biological Chemistry, St. Petersburg State Pediatric Medical University, Litovskaya St. 2, 194100 St. Petersburg, Russia
Abstract
Human serum albumin (HSA) is a multifunctional protein whose biological properties are determined not only by its amino acid sequence but also by a complex interplay of functional sites, post-translational modifications, and endogenous ligands. However, the structural mechanisms by which these regulatory factors influence the functional state of HSA remain insufficiently understood. The aim of this study was to investigate the structural basis of the interplay between HSA functional regions, using Cys34 S-nitrosylation and fatty acid (FA) binding as model regulatory processes. For this purpose, the structural features and conformational dynamics of FA-free and FA-loaded native and nitrosylated HSA, as well as their interactions with glutathione (GSH) and S-nitrosoglutathione (GSNO), were studied using molecular docking and molecular dynamics (MD) simulations. Changes in the overall structure of HSA after incubation with GSNO were assessed by 1H NMR spectroscopy. MD analysis revealed that FA binding alters the conformational dynamics of HSA and affects the structural environment of Cys34 and other functionally significant regions. These FA-induced effects were further modulated by S-nitrosylation, which influenced the conformational landscape of albumin in a manner dependent on its fatty acid-bound state. The similarity of the one-dimensional 1H NMR spectra of HSA before and after incubation with GSNO suggests the absence of pronounced changes in the overall protein structure upon interaction with the nitrosylating agent. The obtained data provide insights into how FA binding and S-nitrosylation shape the conformational properties of HSA through modulation of the structural environment of Cys34 and other functionally significant regions. The results highlight the importance of considering post-translational modifications and endogenous ligands as key determinants of HSA structure–function relationships.
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BibTeX
@article{batalova2026structural,
title = {{Structural Determinants Underlying the Interplay Between Fatty Acid Binding and S-Nitrosylation of Human Serum Albumin}},
author = {Anastasia A. Batalova and Kamila V. Samodurova and Mikhail A. Vovk and Daria A. Belinskaia and Richard O. Jenkins and Nikolay V. Goncharov},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219687},
url = {https://www.mdpi.com/1422-0067/27/21/9687},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Structural Determinants Underlying the Interplay Between Fatty Acid Binding and S-Nitrosylation of Human Serum Albumin
AU - Anastasia A. Batalova
AU - Kamila V. Samodurova
AU - Mikhail A. Vovk
AU - Daria A. Belinskaia
AU - Richard O. Jenkins
AU - Nikolay V. Goncharov
PY - 2026
DA - 2026/10/29
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219687
UR - https://www.mdpi.com/1422-0067/27/21/9687
AB - Human serum albumin (HSA) is a multifunctional protein whose biological properties are determined not only by its amino acid sequence but also by a complex interplay of functional sites, post-translational modifications, and endogenous ligands. However, the structural mechanisms by which these regulatory factors influence the functional state of HSA remain insufficiently understood. The aim of this study was to investigate the structural basis of the interplay between HSA functional regions, using Cys34 S-nitrosylation and fatty acid (FA) binding as model regulatory processes. For this purpose, the structural features and conformational dynamics of FA-free and FA-loaded native and nitrosylated HSA, as well as their interactions with glutathione (GSH) and S-nitrosoglutathione (GSNO), were studied using molecular docking and molecular dynamics (MD) simulations. Changes in the overall structure of HSA after incubation with GSNO were assessed by 1H NMR spectroscopy. MD analysis revealed that FA binding alters the conformational dynamics of HSA and affects the structural environment of Cys34 and other functionally significant regions. These FA-induced effects were further modulated by S-nitrosylation, which influenced the conformational landscape of albumin in a manner dependent on its fatty acid-bound state. The similarity of the one-dimensional 1H NMR spectra of HSA before and after incubation with GSNO suggests the absence of pronounced changes in the overall protein structure upon interaction with the nitrosylating agent. The obtained data provide insights into how FA binding and S-nitrosylation shape the conformational properties of HSA through modulation of the structural environment of Cys34 and other functionally significant regions. The results highlight the importance of considering post-translational modifications and endogenous ligands as key determinants of HSA structure–function relationships.
SN - 1422-0067
ER -