Étude par modélisation moléculaire de systèmes multienzymatiques impliqués dans la biosynthèse des flavonoïdes

Abstract : Flavonoids, some natural compounds exhibiting antioxidant properties, are synthesized along enzymatic cascades involving several enzymes. It has been recently proposed that some of these enzymes are involved in the formation of large transient macromolecular edifices, called metabolon, interacting with cellular membrane. Such molecular complexes should allow direct metabolites transfer from one active site to the other (substrate channeling phenomenon), minimizing diffusion time and solvation effects. The present work aims to establish a first model of a metabolon involving 3 enzymes of the flavonoid biosynthesis: the dihydroflavonol 4-reductase (DFR), the flavonoid 3'-hydroxylase (F3'H) and the leucoanthocyanidin reductase (LAR). The study of such large molecular system requires a multiscale approach based on i) hybrid QM/MM methods to decipher enzymatic mechanism, ii) molecular dynamic simulations in microsecond timescale to estimate thermodynamic and kinetic properties and iii) protein-protein docking at coarse-grained resolution. These different levels of theory allow us to establish a first model of a three-enzymes-metabolon in interaction with a model of cellular membrane.
Document type :
Theses
Complete list of metadatas

Cited literature [176 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-01134421
Contributor : Abes Star <>
Submitted on : Monday, March 23, 2015 - 3:19:35 PM
Last modification on : Thursday, May 3, 2018 - 1:09:24 PM
Long-term archiving on : Thursday, July 2, 2015 - 6:28:43 AM

File

2014NICE4095.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-01134421, version 1

Collections

Citation

Julien Diharce. Étude par modélisation moléculaire de systèmes multienzymatiques impliqués dans la biosynthèse des flavonoïdes. Autre. Université Nice Sophia Antipolis, 2014. Français. ⟨NNT : 2014NICE4095⟩. ⟨tel-01134421⟩

Share

Metrics

Record views

622

Files downloads

2639