The role of astaxanthin‐Cu2+ in stabilizing glycated human serum albumin for type 2 diabetes mellitus management: a computational approach

Naufal Abiyyu; Alfia Fitrianita; I Made Artika; Josephine Elizabeth Siregar; Syahputra Wibowo; Bantari Wisynu Kusuma Wardhani; Canggih Setya Budi; Tri Rini Nuringtyas

doi:10.22146/ijbiotech.109830

The role of astaxanthin‐Cu2+ in stabilizing glycated human serum albumin for type 2 diabetes mellitus management: a computational approach

https://doi.org/10.22146/ijbiotech.109830

Naufal Abiyyu⁽¹⁾, Alfia Fitrianita⁽²⁾, I Made Artika⁽³⁾, Josephine Elizabeth Siregar⁽⁴⁾, Syahputra Wibowo⁽⁵⁾, Bantari Wisynu Kusuma Wardhani⁽⁶⁾, Canggih Setya Budi⁽⁷⁾, Tri Rini Nuringtyas^(8*)

(1) Department of Biochemistry, Faculty of Mathematics and Natural Sciences, Bogor Agricultural University, Dramaga Campus, Bogor, 16680, Indonesia
(2) Biotechnology study program, Postgraduate school, Bogor Agricultural University, Dramaga Campus, Bogor, 16680, Indonesia
(3) Department of Biochemistry, Faculty of Mathematics and Natural Sciences, Bogor Agricultural University, Dramaga Campus, Bogor, 16680, Indonesia
(4) Eijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Cibinong, Bogor, 16911, Indonesia
(5) Eijkman Research Center for Molecular Biology, National Research and Innovation Agency (BRIN), Cibinong, Bogor, 16911, Indonesia
(6) Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency (BRIN), Bogor, Indonesia
(7) Research Center for Polymer Technology, National Research and Innovation Agency (BRIN), The B.J. Habibie Science and Technology Area, South Tangerang, Banten 15314, Indonesia
(8) Department of Tropical Biology, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, Indonesia
(*) Corresponding Author

Abstract

Type 2 diabetes mellitus (T2DM) leads to the non‐enzymatic glycation of proteins, resulting in the formation of advanced glycation end products (AGEs), which contribute to diabetic complications. Human serum albumin (HSA), a major plasma protein, undergoes structural alterations upon glycation (gHSA), reducing its stability and biological functions. Astaxanthin (ASX), a potent antioxidant, is limited by its instability and moderate binding affinity. In this study, we explore the use of copper (Cu²⁺) to form a stable ASX‐Cu²⁺ complex, enhancing the antioxidant properties of ASX and improving its interaction with HSA and gHSA. Utilizing computational approaches such as molecular docking, molecular dynamics (MD) simulations, and free energy landscape (FEL) mapping, we analyze the stability and conformational changes of HSA and gHSA upon binding with ASX and ASX‐Cu²⁺. The residue interaction network (RIN) analysis reveals that ASX‐Cu²⁺ complexes create a more robust and interconnected network of non‐covalent interactions, particularly enhancing hydrogen bonding, π‐stacking, and ionic interactions. The ASX‐Cu²⁺ complex at a 1:2 molar ratio significantly improved the binding affinity and structural stability of both native and glycated HSA, reducing protein fluctuations and promoting a more compact conformation. These findings suggest that ASX‐Cu²⁺ complexes offer therapeutic potential for stabilizing albumin under glycation‐induced stress, with implications for managing oxidative stress and diabetes‐related complications.

Keywords

Astaxanthin, Cu2+, Diabetes mellitus, T2DM, gHSA

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DOI: https://doi.org/10.22146/ijbiotech.109830