Human serum albumin (HSA) - Sudlow's site I (HSA site I)

Human serum albumin (HSA) is the most abundant protein in human blood plasma and serves as a primary carrier for a wide range of endogenous and exogenous compounds [2, 16]. Sudlow's site I, located in subdomain IIA of HSA, is one of the two primary drug-binding sites on the protein and is characterized as a large, flexible hydrophobic cavity [1, 14]. This site preferentially binds bulky heterocyclic anions, such as the anticoagulant warfarin and various non-steroidal anti-inflammatory drugs (NSAIDs) [5, 8]. The binding of drugs to site I significantly influences their pharmacokinetics, including distribution, half-life, and the concentration of the free, pharmacologically active form in the systemic circulation [2, 6]. Competitive displacement at this site by other drugs or endogenous ligands like bilirubin can lead to significant drug-drug interactions and potential toxicity, particularly for drugs with a narrow therapeutic index [5, 7]. Furthermore, physiological conditions such as hypoalbuminemia or the glycation of albumin in diabetes can alter the binding capacity of site I, necessitating dosage adjustments in clinical practice [11, 13].

Other names

Sudlow's site IWarfarin binding siteSubdomain IIA binding siteHSA site I

Reversible binding of bulky heterocyclic anions and other ligands to a large hydrophobic cavity in subdomain IIA, facilitating systemic transport and modulating free drug concentration [1, 2, 14].