• DOI:10.1111/j.1423-0410.2002.tb05326.x
• Corpus ID: 44482133

Beyond Expansion: Structural Studies on the Transport Roles of Human Serum Albumin

@article{Curry2002BeyondES,
  title={Beyond Expansion: Structural Studies on the Transport Roles of Human Serum Albumin},
  author={Stephen Curry},
  journal={Vox Sanguinis},
  year={2002},
  volume={83}
}

• S. Curry
• Published 1 August 2002
• Chemistry, Biology
• Vox Sanguinis

Introduction Clinically, human serum albumin (HSA) is best known as a volume expander but its prominent role in this capacity perhaps overshadows the protein’s other major talent: transport. As a plasma transporter molecule HSA displays truly bewildering binding capabilities. Its primary physiological ligands are non-esterified long-chain fatty acids but HSA also binds toxic metabolites such as bilirubin and CMPF, steroid hormones, thyroxine, tryptophan and several vitamins and metal ions, facilitating their movement around the body or delivery to sites of disposal’. The natural capacity of HSA for a range of endogenous compounds means that the protein is also able to bind a wide variety of drug molecules including chlorpropamide, diazepam, ibuprofen, indomethacin, naproxen and warfarin. The protein can thus have a dramatic effect on the pharmacokinetics and pharmacodynamics of such agents. The broad binding specificity of albumin has intrigued researchers for decades and stimulated wide-ranging investigations in both basic and clinical sciences which aimed to probe the interactions of HSA with its endogenous ligands and to better understand the impact of the protein on various drug therapies. More recently, efforts have been made to exploit the binding properties of HSA to develop it as a novel delivery vehicle for drugs2 or oxygen’, to modulate drug pharmac~dynamics~ or to use the protein to effect chiral separations’. In order to understand and exploit the binding capacity of HSA more fully, detailed structural information on ligand binding to the protein is required. In recent years my group has been applying protein crystallographic methods in order to determine the structure of HSA and a range of HSA-ligand complexes at essentially atomic resolutionbii. Our work to date has focused on structural analysis of HSA complexes with saturated and unsaturated fatty acids, the hormone thyroxine and a range of drug molecules. These investigations have yielded a range of new insights into the way that HSA accommodates endogenous and exogenous ligands; one of the most interesting issues that we can address with this approach is the extent to which different ligands may variously compete or cooperate in their binding to sites on the protein.