Crystallographic analysis of the ternary complex of octanoate and N-acetyl-L-methionine with human serum albumin reveals the mode of their stabilizing interactions

Akito Kawai, Victor T.G. Chuang, Yosuke Kouno, Keishi Yamasaki, Shuichi Miyamoto, Makoto Anraku, Masaki Otagiri

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

During pasteurization and storage of albumin products, Sodium octanoate (Oct) and N-acethyl-L-tryptophan (N-AcTrp) are used as the thermal stabilizer and the antioxidant for human serum albumin (HSA), respectively. We recently reported that N-acethyl-L-methionine (N-AcMet) is an antioxidant for HSA, which is superior to N-AcTrp when it is especially exposed to light during storage. The objective of the present study is to clarify the molecular mechanism responsible for the HSA protective effect of Oct and N-AcMet based on their ternary complex structure. Crystal structure of the HSA–Oct–N-AcMet complex showed that one N-AcMet molecule is bound to the entrance of drug site 1 of HSA, and its side chain, which is susceptible to the oxidation, is exposed to the solvent. At the same time, two Oct binding sites are observed in drug sites 1 and 2 of HSA, respectively, and each Oct molecule occupies the hydrophobic cavity in them. These results indicate the molecular mechanism responsible for the HSA stabilization by these small molecules as follows. N-AcMet seals the entrance of drug site 1 while it acts as an antioxidant for HSA. Oct is chiefly bound to drug site 2 of HSA and it increases the thermal stability of HSA because of the occupying the largest intra-cavity of sub-domain IIIA in HSA. These findings suggest that N-AcMet acts positively as useful stabilizer for albumin formulated products such as functionalized HSA and HSA fusion proteins.

Original languageEnglish
Pages (from-to)979-984
Number of pages6
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1865
Issue number8
DOIs
Publication statusPublished - 08-2017

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

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