Human serum albumin (HSA) subdomain IIIA (HSA subdomain IIIA)

Human serum albumin (HSA) subdomain IIIA, also known as Sudlow's site II, is a major drug-binding region within the most abundant protein in human plasma [1, 4]. This subdomain features a large hydrophobic pocket that preferentially accommodates aromatic compounds and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen [1, 8]. By reversibly binding these ligands, subdomain IIIA plays a pivotal role in determining the pharmacokinetics of numerous drugs, influencing their distribution, metabolism, and excretion [4, 8]. Beyond its role in drug transport, this region is involved in the binding of endogenous substances like long-chain fatty acids and hormones [1, 10]. In clinical practice, HSA is utilized as a drug delivery vehicle to improve the solubility and half-life of therapeutic agents, particularly in oncology [3, 4]. The subdomain's structure is stabilized by multiple disulfide bridges and is sensitive to post-translational modifications like glycation, which can alter its binding affinity [1, 7]. However, the high affinity of this site for multiple drugs can lead to competitive displacement, potentially causing adverse effects or altered efficacy [1, 4]. Understanding the molecular interactions at subdomain IIIA is crucial for predicting drug-drug interactions and optimizing therapeutic dosing [4, 13].

Other names

Sudlow's site IISite IIDomain III subdomain AHSA-IIIA

Reversible binding to the Sudlow site II hydrophobic pocket, which modulates the pharmacokinetic profile of drugs by extending circulatory half-life and regulating the free drug fraction [1, 4].