Human serum albumin (HSA), site I (HSA)

Human serum albumin (HSA) is the most prevalent protein in human plasma, accounting for approximately 50-60% of total protein content. It is a single-chain non-glycosylated polypeptide synthesized by the liver, primarily responsible for maintaining colloid osmotic pressure and transporting various endogenous and exogenous substances, including fatty acids, hormones, and drugs (UniProt: P02768). Site I, also known as Sudlow's site I or the warfarin-binding site, is located within subdomain IIA and is characterized by a large, flexible hydrophobic pocket that accommodates bulky heterocyclic anions (PubMed: 11013345). Binding at this site significantly dictates the pharmacokinetic profile of many therapeutic agents, as only the unbound fraction of a drug is pharmacologically active. Consequently, competition for Site I can lead to significant drug-drug interactions, where one drug displaces another, potentially increasing the free concentration and risk of toxicity (StatPearls: NBK459132). Understanding the structural basis of drug binding at Site I is essential for predicting drug distribution and potential adverse reactions in clinical practice (PubMed: 15913176).

Other names

Sudlow's site IWarfarin-azapropazone binding siteSubdomain IIAAlbumin site IALB

Reversible binding of bulky heterocyclic anions to a hydrophobic pocket in subdomain IIA, which modulates the free concentration, volume of distribution, and elimination kinetics of the ligand.