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

DOI PDF Web Site PubMed 3 Citations 45 References
  • 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

Bibliographic Information

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

Search this article

Abstract

The pKa 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 pKa value became [e. g., 7.4 (8-NH2-FAD) and 4.0 (8-CN-FAD)], suggesting that the flavin ring itself affects the pKa 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 pKa by ca. 2.5 units. These results indicate that the interaction between the ligand and the flavin ring also serves to lower the pKa of the ligand, in addition to the hydrogen bonds at C(1)=O of the ligand.

Journal

Citations (3)*help

See more

References(45)*help

See more

Keywords

Details 詳細情報について

Report a problem

Back to top