Theoretical analyses of the fluorescence lifetimes of the<scp>d</scp>-amino acid oxidase–benzoate complex dimer from porcine kidney: molecular dynamics simulation and photoinduced electron transfer

Nueangaudom, Arthit; Lugsanangarm, Kiattisak; Pianwanit, Somsak; Kokpol, Sirirat; Nunthaboot, Nadtanet; Tanaka, Fumio; Taniguchi, Seiji; Chosrowjan, Haik

doi:10.1039/c4ra05211k

Cited by 12 publications

(20 citation statements)

References 59 publications

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“…The catalytic pockets dynamic revealed to be rather different from the crystallographic data in both wt proteins, more pronounced in the side‐chain conformations of the catalytic residue E376 and R256 residue in the presence of the fatty‐acyl substrate. Differences between the crystallographic and the MD structures have been also reported in other flavoproteins .…”

Section: Discussionmentioning

confidence: 77%

Insights into Medium‐chain Acyl‐CoA Dehydrogenase Structure by Molecular Dynamics Simulations

et al. 2016

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The medium-chain acyl-CoA dehydrogenase (MCAD) is a mitochondrial enzyme that catalyzes the first step of mitochondrial fatty acid β-oxidation (mFAO) pathway. Its deficiency is the most common genetic disorder of mFAO. Many of the MCAD disease-causing variants, including the most common p.K304E variant, show loss of function due to protein misfolding. Herein, we used molecular dynamics simulations to provide insights into the structural stability and dynamic behavior of MCAD wild-type (MCADwt) and validate a structure that would allow reliable new studies on its variants. Our results revealed that in both proteins the flavin adenine dinucleotide (FAD) has an important structural role on the tetramer stability and also in maintaining the volume of the enzyme catalytic pockets. We confirmed that the presence of substrate changes the dynamics of the catalytic pockets and increases FAD affinity. A comparison between the porcine MCADwt (pMCADwt) and human MCADwt (hMCADwt) structures revealed that both proteins are essentially similar and that the reversion of the double mutant E376G/T255E of hMCAD enzyme does not affect the structure of the protein neither its behavior in simulation. Our validated hMCADwt structure is crucial for complementing and accelerating the experimental studies aiming for the discovery and development of potential stabilizers of MCAD variants as candidates for the treatment of MCAD deficiency (MCADD).

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Section: Discussionmentioning

confidence: 77%

Insights into Medium‐chain Acyl‐CoA Dehydrogenase Structure by Molecular Dynamics Simulations

et al. 2016

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“…In the crystal the two subunits were almost completely equivalent (Suto et al, 2000;Taniguchi et al, 2013). In the D-amino acid oxidase (DAAO) from porcine kidney À benzoate complex (DAOB) dimer, it was also found that the structures of the two subunits near Iso were not equivalent, as revealed by the MDS technique (Nueangaudom et al, 2014a), which was predicted by experimental work on the fluorescence dynamics . In the crystal, the two subunits in the DAOB dimer were almost equivalent (Nueangaudom et al, 2014a;Mizutani et al, 1996).…”

Section: Discussionmentioning

confidence: 94%

“…In the D-amino acid oxidase (DAAO) from porcine kidney À benzoate complex (DAOB) dimer, it was also found that the structures of the two subunits near Iso were not equivalent, as revealed by the MDS technique (Nueangaudom et al, 2014a), which was predicted by experimental work on the fluorescence dynamics . In the crystal, the two subunits in the DAOB dimer were almost equivalent (Nueangaudom et al, 2014a;Mizutani et al, 1996). Pyranose 2-oxidase from Trametes multicolor is a tetramer, and an ultrafast fluorescence dynamics experiment revealed that there exist two lifetime components, 0.88 ps and 360 ps, which shows that the protein structure near Iso is extremely heterogeneous Taniguchi et al, 2012).…”

Section: Discussionmentioning

confidence: 95%

“…In these works, however, the protein structures were assumed to be similar between the two subunits in the dimers as in the crystal structures. Recently, it has been demonstrated by means of ultrafast fluorescence spectroscopy and ET analyses that the subunit structures are not equivalent between two subunits in D-amino acid oxidase À benzoate complex (DAOB) dimer Nueangaudom et al, 2014a), and among the four subunits in pyranose 2-oxidase Taniguchi et al, 2012;Lugsanangarm et al, 2014Lugsanangarm et al, , 2015. It is very important to examine whether the two subunits in FBP dimers are equivalent in solution, to understand the precise mechanisms of the ET.…”

Section: Introductionmentioning

confidence: 99%

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Conformational difference between two subunits in flavin mononucleotide binding protein dimers from Desulfovibrio vulgaris (MF): molecular dynamics simulation

Nunthaboot

Lugsanangarm

Pianwanit

et al. 2016

Computational Biology and Chemistry

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“…The SHAKE algorithm [52] was employed to constrain all bonds involving hydrogen atoms. Details of the methods are described elsewhere [53][54][55][56].…”

Section: Mds Calculationsmentioning

confidence: 99%

New Aspects of the Structure of d-Amino Acid Oxidase from Porcine Kidney in Solution: Molecular Dynamics Simulation and Photoinduced Electron Transfer

Nueangaudom¹,

Lugsanangarm²,

Pianwanit³

et al. 2017

Amino Acid - New Insights and Roles in Plant and Animal

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Mammalian D-amino acid oxidase (DAAO) plays an important role for D-serine metabolism in the brain and regulation of glutamatergic neurotransmission. In the present work, the structures in solution obtained by the methods of molecular dynamic simulation (MDS) and analyses of photoinduced electron transfer (ET) from aromatic amino acids to the excited isoalloxazine (Iso*) are described based upon our recent works, comparing among DAAO dimer, monomer, DAAO-benzoate (DAOB) complex dimer and monomer. The fluorescence lifetimes of DAAO and DAOB in the time domain of picoseconds and femtoseconds are used for the ET analyses as experimental data. The ET parameters (static dielectric constants near isoalloxazine (Iso), standard free energy gap (SFEG) between the photoproducts and reactants), ET rates, and related physical quantities (solvent reorganization energy, net electrostatic energy between the photoproducts and ionic groups in the proteins), in addition to MDS structures, are used to compare the protein structures. The structure of the DAOB dimer in solution obtained by MDS is substantially different from the crystal structure, and the structures of the two subunits are not equivalent in solution. The ET rates and related physical quantities also differ between the two subunits. Keywords: D-amino acid oxidase from porcine kidney, benzoate complex, molecular dynamics simulation, dimer and monomer structures in solution, analyses of photoinduced electron transfer, rate of photoinduced electron transfer, fluorescence lifetimes

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Theoretical analyses of the fluorescence lifetimes of thed-amino acid oxidase–benzoate complex dimer from porcine kidney: molecular dynamics simulation and photoinduced electron transfer

Abstract: The mechanism of photoinduced electron transfer from benzoate and aromatic amino acids to the excited isoalloxazine in the d-amino acid oxidase–benzoate complex dimer was studied using molecular dynamics simulation and an electron transfer theory.

Cited by 12 publications

References 59 publications

Insights into Medium‐chain Acyl‐CoA Dehydrogenase Structure by Molecular Dynamics Simulations

Insights into Medium‐chain Acyl‐CoA Dehydrogenase Structure by Molecular Dynamics Simulations

Conformational difference between two subunits in flavin mononucleotide binding protein dimers from Desulfovibrio vulgaris (MF): molecular dynamics simulation

New Aspects of the Structure of d-Amino Acid Oxidase from Porcine Kidney in Solution: Molecular Dynamics Simulation and Photoinduced Electron Transfer

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