Molecular mechanism of the drop in the pKa of a substrate analog bound to medium-chain acyl-CoA dehydrogenase: implications for substrate activation.

Molecular mechanism of the drop in the pKa of a substrate analog bound to medium-chain acyl-CoA dehydrogenase: implications for substrate activation. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Molecular mechanism of the drop in the pKa of a substrate analog bound to medium-chain acyl-CoA dehydrogenase: implications for substrate activation. Abstract Text:

Yasuzo Nishina,Kyosuke Sato,Haruhiko Tamaoki,Takeyuki Tanaka,Chiaki Setoyama,Retsu Miura,Kiyoshi Shiga,

The pKa value of a substrate analogue 3-thiaoctanoyl-CoA at alphaC-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.

Molecular mechanism of the drop in the pKa of a substrate analog bound to medium-chain acyl-CoA dehydrogenase: implications for substrate activation. Publishing Authors By Initials

Y Nishina,K Sato,H Tamaoki,T Tanaka,C Setoyama,R Miura,K Shiga,

For similar animals: chordata: vertebrates: mammals: artiodactyla: swine research abstracts see: animals: chordata: vertebrates: mammals: artiodactyla: swine research

PUBMED ID PMID:

MEDLINE DATE:

Molecular mechanism of the drop in the pKa of a substrate analog bound to medium-chain acyl-CoA dehydrogenase: implications for substrate activation. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of biochemistry

VOLUME: 134

Page Numbers: 835-42

Journal Abbreviation: J. Biochem.

ISSN: 0021-924X

DAY: 19

MONTH: Dec

YEAR: 2003

Molecular mechanism of the drop in the pKa of a substrate analog bound to medium-chain acyl-CoA dehydrogenase: implications for substrate activation. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 376600

Molecular mechanism of the drop in the pKa of a substrate analog bound to medium-chain acyl-CoA dehydrogenase: implications for substrate activation. Keywords Mesh Terms:

KEYWORDS: Swine

MESH TERMS: chemistry

Chemical & Substance for Abstract: Molecular mechanism of the drop in the pKa of a substrate analog bound to medium-chain acyl-CoA dehydrogenase: implications for substrate activation. Information

Substance Name: Acyl-CoA Dehydrogenase

Registry Number: EC 1.3.99.3

Grant and Affiliation Information for Molecular mechanism of the drop in the pKa of a substrate analog bound to medium-chain acyl-CoA dehydrogenase: implications for substrate activation.

AFFILIATION: Department of Molecular Physiology, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto 860-8556. nishina@medic.kumamoto-u.ac.jp

Country: Japan

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: J Biochem

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Molecular mechanism of the drop in the pKa of a substrate analog bound to medium-chain acyl-CoA dehydrogenase: implications for substrate activation Related Publications

• 13C- and 15N-NMR studies on medium-chain acyl-CoA dehydrogenase reconstituted with 13C- and 15N-enriched flavin adenine dinucleotide.
• A resonance Raman study on a reaction intermediate of Pseudomonas L-phenylalanine oxidase (deaminating and decarboxylating).
• A resonance Raman study on the structures of complexes of flavoprotein D-amino acid oxidase.
• Analysis of the visible absorption and circular dichroism spectra of D-amino-acid oxidase complexes.
• Anion-induced conformational change of apo-electron-transferring flavoprotein.
• C-NMR study on the interaction of medium-chain acyl-CoA dehydrogenase with acetoacetyl-CoA.
• Complex formation between anionic semiquinoid form of a flavoenzyme D-amino acid oxidase and ligands. Stabilizing mechanism of anionic semiquinoid flavoenzyme.
• Complex formation between reduced D-amino acid oxidase and pyridine carboxylates.
• Dorsal root ganglion regulates the transient ERK activation in the dorsal horn of the spinal cord during development.
• Effect of cholesterol on human erythrocyte membrane. A spin label study.
• Effects of pH and ionic strength on the binding of egg white riboflavin binding protein with flavins.
• Electron-transferring flavoprotein has an AMP-binding site in addition to the FAD-binding site.
• In vitro assembly of FAD, AMP, and the two subunits of electron-transferring flavoprotein: an important role of AMP related with the conformational change of the apoprotein.
• In vitro refolding and unfolding of subunits of electron-transferring flavoprotein: characterization of the folding intermediates and the effects of FAD and AMP on the folding reaction.
• Intramolecular and intermolecular perturbation on electronic state of FAD free in solution and bound to flavoproteins: FTIR spectroscopic study by using the C = O stretching vibrations as probes.
• Isomerization of delta 1-piperideine-2-carboxylate to delta 2-piperideine-2-carboxylate on complexation with flavoprotein D-amino acid oxidase.
• Kinetic and equilibrium studies on the interaction of reduced flavoprotein D-amino acid oxidase with pyridine carboxylates.
• Molecular mechanism of the drop in the pKa of a substrate analog bound to medium-chain acyl-CoA dehydrogenase: implications for substrate activation.
• On the ligands in charge-transfer complexes of porcine kidney flavoenzyme D-amino acid oxidase in three redox states: a resonance Raman study.
• Peptide immunocytochemistry of neurons projecting to the retrocerebral complex in the blow fly, Protophormia terraenovae.
• Preparation of separated alpha and beta subunits of electron-transferring flavoprotein in unfolded forms and their restoration to the native holoprotein form.
• Proton release from flavoprotein D-amino acid oxidase on complexation with the zwitterionic ligand, trigonelline.
• Purification of electron-transferring flavoprotein from Megasphaera elsdenii and binding of additional FAD with an unusual absorption spectrum.
• Resonance Raman spectra of anionic semiquinoid form of a flavoenzyme, D-amino acid oxidase.
• Spectroscopic studies of rat liver acyl-CoA oxidase with reference to recognition and activation of substrate.
• Structural modulation of 2-enoyl-CoA bound to reduced acyl-CoA dehydrogenases: a resonance Raman study of a catalytic intermediate.
• Structures of charge-transfer complexes of flavoenzyme D-amino acid oxidase: a study by resonance Raman spectroscopy and extended Hückel molecular orbital method.
• Substrate activating mechanism of short-chain acyl-CoA, medium-chain acyl-CoA, long-chain acyl-CoA, and isovaleryl-CoA dehydrogenases from bovine liver: a resonance Raman study on the 3-ketoacyl-CoA complexes.
• Substrate recognition and activation mechanism of D-amino acid oxidase: a study using substrate analogs.
• The binding of adenine nucleotides to apo-electron-transferring flavoprotein.