Molecular Mechanism of the Drop in the pKa of a Substrate Analog Bound to Medium-Chain Acyl-CoA Dehydrogenase: Implications for Substrate Activation

• Nishina Yasuzo

  Department of Molecular Physiology Graduate School of Medical Sciences, Kumamoto University

• Sato Kyosuke

  Department of Molecular Physiology Graduate School of Medical Sciences, Kumamoto University

• Tamaoki Haruhiko

  Department of Molecular Enzymology, Graduate School of Medical Sciences, Kumamoto University

• Tanaka Takeyuki

  Division of Biological Chemistry, Department of Life Science, Graduate School of Science and Technology, Kobe University

• Setoyama Chiaki

  Department of Molecular Enzymology, Graduate School of Medical Sciences, Kumamoto University

• Miura Retsu

  Department of Molecular Enzymology, Graduate School of Medical Sciences, Kumamoto University

• Shiga Kiyoshi

  Department of Molecular Physiology Graduate School of Medical Sciences, Kumamoto University

書誌事項

タイトル別名

• Molecular Mechanism of the Drop in the p<i>K</i>_a of a Substrate Analog Bound to Medium-Chain Acyl-CoA Dehydrogenase: Implications for Substrate Activation

抄録

The pK_a value of a substrate analogue 3-thiaoctanoyl-CoA at αC-H is known to drop from ca. 16 in the free state to 5-6 upon binding to medium-chain acyl-CoA dehydrogenase (MCAD). The molecular mechanism underlying this phenomenon was investigated by taking advantage of artificial FADs, i.e., 8-CN-, 7, 8-Cl₂-, 8-Cl-, 8-OCH₃-, 8-NH₂-, ribityl-2'-deoxy-8-CN-, and ribityl-2'-deoxy-8-Cl-FADs, reconstituted into MCAD. The stronger the electron-withdrawing ability of the substituent, the smaller the pK_a value became [e. g., 7.4 (8-NH₂-FAD) and 4.0 (8-CN-FAD)], suggesting that the flavin ring itself affects the pK_a value of the ligand via a charge-transfer interaction with the ligand. The destruction of the hydrogen bond between the thioester C(1)=O and the ribityl-2'-OH of FAD raised the pK_a by ca. 2.5 units. These results indicate that the interaction between the ligand and the flavin ring also serves to lower the pK_a of the ligand, in addition to the hydrogen bonds at C(1)=O of the ligand.

収録刊行物

• The Journal of Biochemistry

  The Journal of Biochemistry 134 (6), 835-842, 2003

  社団法人 日本生化学会

キーワード

• acyl-CoA dehydrogenase
• artificial flavin
• charge-transfer complex
• flavoenzyme
• hydrogen bond

詳細情報

• CRID: 1390001204964833408
• NII論文ID: 130003534635
• NII論文ID: 10012059796
• NII書誌ID: AA00694073
• DOI: 10.1093/jb/mvg209
• COI: 1:CAS:528:DC%2BD2cXis1Kks74%3D
• ISSN: 17562651
• ISSN: 0021924X
• NDL書誌ID: 6830750
• PubMed: 14769872
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I6830750
• Web Site: http://academic.oup.com/jb/article-pdf/134/6/835/2380885/mvg209.pdf
• Web Site: https://search.jamas.or.jp/link/ui/2004130088
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可