The article by Xiao Min He and Daniel C. Carter provides a detailed analysis of the three-dimensional structure of human serum albumin (HSA) determined by crystallography at a resolution of 2.8 Å. HSA is composed of three homologous domains that form a heart-shaped molecule. The structure reveals that the principal regions for ligand binding are located in hydrophobic cavities within subdomains IIA and IIIA, which exhibit similar chemistry. The study explains various physical phenomena and offers insights into future pharmacokinetic and genetically engineered therapeutic applications of serum albumin. The authors also discuss the ligand binding chemistry, highlighting the importance of specific residues such as Trp 214, Lys 199, and Tyr 411 in the binding process. The crystal structure of HSA and its recombinant form (rHSA) is determined using isomorphous replacement and molecular replacement methods, respectively. The article concludes by discussing the implications of the structure for understanding and predicting ligand displacement interactions and for potential modifications to enhance binding activities for therapeutic or diagnostic purposes.The article by Xiao Min He and Daniel C. Carter provides a detailed analysis of the three-dimensional structure of human serum albumin (HSA) determined by crystallography at a resolution of 2.8 Å. HSA is composed of three homologous domains that form a heart-shaped molecule. The structure reveals that the principal regions for ligand binding are located in hydrophobic cavities within subdomains IIA and IIIA, which exhibit similar chemistry. The study explains various physical phenomena and offers insights into future pharmacokinetic and genetically engineered therapeutic applications of serum albumin. The authors also discuss the ligand binding chemistry, highlighting the importance of specific residues such as Trp 214, Lys 199, and Tyr 411 in the binding process. The crystal structure of HSA and its recombinant form (rHSA) is determined using isomorphous replacement and molecular replacement methods, respectively. The article concludes by discussing the implications of the structure for understanding and predicting ligand displacement interactions and for potential modifications to enhance binding activities for therapeutic or diagnostic purposes.