6EZQ

human Serum Albumin complexed with NBD-C12 fatty acid

Summary for 6EZQ

• Entry DOI: 10.2210/pdb6ezq/pdb
• Descriptor: Serum albumin, 12-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]dodecanoic acid (3 entities in total)
• Functional Keywords: fatty acid binding site human serum albumin nbd label drug interaction, transport protein
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted: P02768
• Total number of polymer chains: 1
• Total formula weight: 67328.07

Authors

Wenskowsky, L.,Liesum, A.,Schreuder, H.A. (deposition date: 2017-11-16, release date: 2017-12-13, Last modification date: 2024-10-09)

Primary citation

Wenskowsky, L.,Schreuder, H.,Derdau, V.,Matter, H.,Volkmar, J.,Nazare, M.,Opatz, T.,Petry, S.
Identification and Characterization of a Single High-Affinity Fatty Acid Binding Site in Human Serum Albumin.
Angew. Chem. Int. Ed. Engl., 57:1044-1048, 2018

PubMed Abstract: A single high-affinity fatty acid binding site in the important human transport protein serum albumin (HSA) is identified and characterized using an NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl)-C fatty acid. This ligand exhibits a 1:1 binding stoichiometry in its HSA complex with high site-specificity. The complex dissociation constant is determined by titration experiments as well as radioactive equilibrium dialysis. Competition experiments with the known HSA-binding drugs warfarin and ibuprofen confirm the new binding site to be different from Sudlow-sites I and II. These binding studies are extended to other albumin binders and fatty acid derivatives. Furthermore an X-ray crystal structure allows locating the binding site in HSA subdomain IIA. The knowledge about this novel HSA site will be important for drug depot development and for understanding drug-protein interaction, which are important prerequisites for modulation of drug pharmacokinetics.

PubMed: 29193545
DOI: 10.1002/anie.201710437

Experimental method

X-RAY DIFFRACTION (2.39 Å)