Serum albumin (Sudlow's site II) (HSA)

Serum albumin is the most abundant protein in human plasma, serving as the primary carrier for various endogenous and exogenous compounds (UniProt KB - P02768). Sudlow's site II, located within subdomain IIIA, is one of the two primary drug-binding sites on the molecule and is often referred to as the indole-benzodiazepine site (Sudlow et al., 1975). This site typically binds small, aromatic carboxylic acids and neutral lipophilic compounds, such as ibuprofen and diazepam (Ghuman et al., 2005). By binding these molecules, albumin regulates their free plasma concentration, half-life, and overall distribution throughout the body (Petitpas et al., 2001). In clinical contexts, site II is a critical factor in drug-drug interactions, as competition for this site can lead to an increase in the pharmacologically active free fraction of a drug, potentially causing toxicity (Ghuman et al., 2005). Furthermore, alterations in albumin levels due to liver or kidney disease significantly impact the pharmacokinetics of drugs that target this site (UniProt KB - P02768). The site is characterized by a hydrophobic pocket that accommodates ligands through a combination of hydrophobic interactions and hydrogen bonding (Ghuman et al., 2005). Understanding the binding affinity at site II is essential for predicting the volume of distribution and clearance of many non-steroidal anti-inflammatory drugs (NSAIDs) (Petitpas et al., 2001).

Other names

Sudlow's site IIIndole-benzodiazepine siteSubdomain IIIA of albuminHSA site IIAlbumin site 2

Serum albumin site II acts as a high-affinity binding pocket for aromatic carboxylates and benzodiazepines, utilizing a hydrophobic cavity in subdomain IIIA to sequester drugs from the aqueous environment, thereby modulating their bioavailability and systemic half-life (Ghuman et al., 2005; Sudlow et al., 1975).