Naslov
Analysis of glycerol binding within the active site of B12‐dependent diol dehydratase; implications for catalysis and inhibition

Autori
Bilić, Luka ; Barić, Danijela ; Banhatti, Radha Dilip ; Smith, David Matthew ; Kovačević, Borislav

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
26th Croatian meeting of chemists & chemical engineers (HSKIKI)

Mjesto i datum
Šibenik, Hrvatska, 09.04.2019. - 12.04.2019

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Podatak o recenziji nije dostupan

Ključne riječi
B12-dependent diol dehydratase ; Substrate binding ; Glycerol inactivation ; Molecular dynamics ; QM/MM calculations

Sažetak
Microbial conversion of crude glycerol, the waste from biofuel production, into compounds of greater industrial value could solve technical difficulties encountered by the conventional means of chemical conversion [1]. During the particular type of microbial conversion, in the first step glycerol undergoes dehydration by enzymes dehydratases into 3‐hydroxylpropionaldehyde (3HPA) [2, 3]. Two classes of dehydratases can catalyze dehydration of glycerol, B12‐independent and B12‐dependent dehydratases, from which B12‐ dependent class is more often used due to its tolerance to aerobic conditions [4]. However, a peculiar property of B12‐dependent dehydratases is that glycerol, which is their substrate, also acts as an irreversible inhibitor [5]. Based on the B12‐dependent diol dehydratase (B12‐dDDH) crystal structure with glycerol (PDB code: 3AUJ), K. Yoshizawa et al. concluded that the geometry of such bound glycerol enables radical reorganization thus causing inhibition. [6] However, in the recent study on similar enzyme B12‐dependent glycerol dehydratase we observed glycerol in a different geometry [7]. Here we present a detailed computational study of glycerol binding within the active site of B12‐dDDH and find a binding geometry similar to one observed in Ref. 7 (Figure 1). We consider larger implications of our findings for the mechanism of substrate induced inactivation.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA