Human serum albumin (Sudlow's site II) (HSA (Site II))

Human serum albumin (HSA) is the most abundant protein in human blood plasma, functioning as the primary carrier for various endogenous and exogenous molecules [3, 12]. Sudlow's site II, located in subdomain IIIA, is one of the two principal drug-binding pockets on HSA and is specifically known for its affinity for aromatic carboxylates and non-steroidal anti-inflammatory drugs (NSAIDs) [1, 15]. This site plays a critical role in pharmacology by determining the free fraction of drugs such as ibuprofen and diazepam, which in turn dictates their therapeutic efficacy and safety profiles [2, 10]. Binding at Sudlow's site II is mediated by a combination of hydrophobic interactions and hydrogen bonding with key residues like Tyr411 [4, 8]. Pathological conditions such as diabetes can lead to the glycation of HSA, which significantly impairs the binding capacity of Sudlow's site II and may necessitate dosage adjustments [6, 13]. Furthermore, competitive displacement of drugs from this site by other ligands or fatty acids can lead to sudden increases in free drug concentrations, posing a risk for adverse drug-drug interactions [1, 14]. Understanding the structural and functional characteristics of Sudlow's site II is therefore essential for drug design and the management of complex therapeutic regimens [7, 12].

Other names

Sudlow's site IISite IIIbuprofen binding siteSubdomain IIIA binding siteFA3-FA4 binding site

Reversible binding to the hydrophobic pocket in subdomain IIIA of human serum albumin, which regulates the free fraction and systemic distribution of ligands [1, 12].