Tyrosine411 and Arginine410 of Human Serum Albumin Play an Important Role in the Binding of Sodium 4-Phenylbutyrate to Site II.
Sodium 4-phenylbutyrate (PB) has many pharmacological activities; therefore extending its clinical use to the treatment of a wider variety of diseases would be desirable. However, our knowledge of the binding of PB to plasma proteins is not extensive. To address this issue in more detail, we characterized the protein binding of PB. Binding experiments showed that PB mainly binds to human serum albumin (HSA) in plasma. PB was also found to bind to a single site on HSA, which was identified as site II by fluorescent probe displacement experiment. Furthermore, an appropriate alkyl chain length and a carboxylic group in the PB structure were required for PB binding to HSA, suggesting that hydrophobic (and van der Waals) and electrostatic interactions are involved as binding modes. The contributions of hydrogen bonding and/or van der Waals interactions were also indicated by thermodynamic analyses. Tyrosine411 and arginine410 were identified as being involved in the binding of PB to site II, based on binding experiments using chemically modified- and mutant-HSA preparations. In conclusion, the available evidence indicates that PB binds to site II of HSA with assistance by multiple forces and that tyrosine411 and arginine410 both play important roles in this phenomenon.
Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
Taisuke
T
Enokida
Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan; DDS Research Institute, Sojo University, Kumamoto 860-0082, Japan. Electronic address: kcyama@ph.sojo-u.ac.jp.
Keishi
K
Yamasaki
Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
Yuko
Y
Okamoto
Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
Kazuaki
K
Taguchi
Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
Takako
T
Ishiguro
Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Toru
T
Maruyama
Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan; DDS Research Institute, Sojo University, Kumamoto 860-0082, Japan.
Hakaru
H
Seo
Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan; DDS Research Institute, Sojo University, Kumamoto 860-0082, Japan. Electronic address: otagirim@ph.sojo-u.ac.jp.
Masaki
M
Otagiri
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D001120:Arginine / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites / Q000502:physiology; D006801:Humans; D010654:Phenylbutyrates / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D000075462:Serum Albumin, Human / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism*
D000970:Antineoplastic Agents; D010654:Phenylbutyrates; D014443:Tyrosine; C075773:4-phenylbutyric acid; D001120:Arginine; D000075462:Serum Albumin, Human
binding site; human serum albumin; site II; sodium 4-phenylbutyrate