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Human pyruvate dehydrogenase complex E2 and E3BP core subunits: new models and insights from Mmlecular dynamics simulations
Publikationstyp
Journal Article
Date Issued
2016-05-04
Sprache
English
Author(s)
Institut
TORE-URI
Volume
120
Issue
19
Start Page
4399
End Page
4409
Citation
Journal of Physical Chemistry B 19 (120): 4399-4409 (2016-05-19)
Publisher DOI
Scopus ID
Publisher
Soc.
Targeted manipulation and exploitation of beneficial properties of multienzyme complexes, especially for the design of novel and efficiently structured enzymatic reaction cascades, require a solid model understanding of mechanistic principles governing the structure and functionality of the complexes. This type of system-level and quantitative knowledge has been very scarce thus far. We utilize the human pyruvate dehydrogenase complex (hPDC) as a versatile template to conduct corresponding studies. Here we present new homology models of the core subunits of the hPDC, namely E2 and E3BP, as the first time effort to elucidate the assembly of hPDC core based on molecular dynamic simulation. New models of E2 and E3BP were generated and validated at atomistic level for different properties of the proteins. The results of the wild type dimer simulations showed a strong hydrophobic interaction between the C-terminal and the hydrophobic pocket which is the main driving force in the intertrimer binding and the core self-assembly. On the contrary, the C-terminal truncated versions exhibited a drastic loss of hydrophobic interaction leading to a dimeric separation. This study represents a significant step toward a model-based understanding of structure and function of large multienzyme systems like PDC for developing highly efficient biocatalyst or bioreaction cascades.
DDC Class
530: Physik
540: Chemie
600: Technik
More Funding Information
Funding by the German Federal Ministry of Education and Research (BMBF, grant 031A128).