9UPD
Crystal structure of human serum albumin complex with nateglinide
This is a non-PDB format compatible entry.
Summary for 9UPD
Entry DOI | 10.2210/pdb9upd/pdb |
Descriptor | Serum albumin, (2R)-3-phenyl-2-[(4-propan-2-ylcyclohexyl)carbonylamino]propanoic acid, PHOSPHATE ION (3 entities in total) |
Functional Keywords | human serum albumin, nateglinide, complex, transport protein |
Biological source | Homo sapiens (human) |
Total number of polymer chains | 2 |
Total formula weight | 133967.23 |
Authors | Kawai, A.,Nishi, K.,Yamasaki, K. (deposition date: 2025-04-28, release date: 2025-07-16, Last modification date: 2025-09-03) |
Primary citation | Kawai, A.,Nishi, K.,Tokuno, M.,Otagiri, M.,Yamasaki, K. Insights into Dual Binding Modes of Nateglinide to Human Serum Albumin. Acs Med.Chem.Lett., 16:1619-1625, 2025 Cited by PubMed Abstract: Nateglinide is a short-acting insulin secretagogue clinically used for the treatment of type 2 diabetes mellitus. Nateglinide exhibits a high plasma protein binding rate of approximately 98%, primarily binding to subdomain IIIA of human serum albumin (HSA). Here, we determined the crystal structure of the HSA-nateglinide complex at 2.80 Å resolution, revealing dual binding modes of nateglinide within the same binding site. To evaluate the stability of these alternative binding modes, molecular dynamics simulations were conducted, and binding free energies were calculated using the molecular mechanics Poisson-Boltzmann surface area method. The calculated binding free energy values were consistent with experimentally determined data. Our results highlight the structural adaptability of HSA and emphasize the possibility of alternative ligand binding modes existing within a single binding site, as well as the importance of identifying and characterizing these modes to enhance our understanding of drug-plasma protein interactions. PubMed: 40832515DOI: 10.1021/acsmedchemlett.5c00277 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
Download full validation report
