Promotionsvortrag Physik: Computational study of substrate induced inactivation of B12-dependent diol dehydra-tase; Multiscale approach

Ankündigung des Promotionsvortrags von: Herrn Luka Bilic

Enzymatic recycling of crude glycerol (a major biodiesel byproduct) is limited by substrate-induced inactivation of B12-dependent dehydratases. This presentation reports a multiscale computational study of B12-dependent diol dehydratase (B12-dDDH) with multiple substrates and, where possi-ble, comparison to oxygen sensitive B12-independent glycerol dehydratase (B12-iGDH). Molecu-lar-dynamics simulations reveal an alternative glycerol binding mode with the C3-OH oriented to-ward Asp335 rather than Ser301; QM/MM (ONIOM) calculations show this mode is energetically favored in biologically active B12-dDDH. In this alternative binding mode C1 and C3 hydrogen abstraction are competitive to each other.

Reaction profiles indicate a chiral preference where (S)-complexes favor C3 H-abstraction and (R)-complexes favor C1 H-abstraction. C3 abstraction traps glycerol radical intermediate in poten-tial energy well causing irreversible inactivation; in contrast, the analogous pathway is reversible in B12-iGDH. Finally, 3,3,3-trifluoro-1,2-propanediol (F3PDO) is characterized as a slow substrate that can act as a reversible inactivator via steric hindrance of the hydrogen re-abstraction.

The results explore irreversible and reversible substrate induced inactivation of B12-dDDH and propose novel irreversible inactivation mechanism consistent with experimental findings.

(Vortrag auf Englisch)

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