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Pregled bibliografske jedinice broj: 949496

Computational Tale of Two Enzymes: Glycerol Dehydration With or Without B12

Kovačević, Borislav; Barić, Danijela; Babić, Darko; Bilić, Luka; Hanževački, Marko; Sandala, Gregory M.; Radom, Leo; Smith, David M.
Computational Tale of Two Enzymes: Glycerol Dehydration With or Without B12 // Journal of the American Chemical Society, 140 (2018), 27; 8487-8496 doi:10.1021/jacs.8b03109 (međunarodna recenzija, članak, znanstveni)

Computational Tale of Two Enzymes: Glycerol Dehydration With or Without B12

Kovačević, Borislav ; Barić, Danijela ; Babić, Darko ; Bilić, Luka ; Hanževački, Marko ; Sandala, Gregory M. ; Radom, Leo ; Smith, David M.

Journal of the American Chemical Society (0002-7863) 140 (2018), 27; 8487-8496

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
B12-dependent GDH ; B12-indipendent B12 ; QM/MM ; mechanism of catalysis

We present a series of QM/MM calculations aimed at understanding the mechanism of the biological dehydration of glycerol. Strikingly and unusually, this process is catalyzed by two different radical enzymes, one of which is a coenzyme-B12-dependent enzyme and the other which is a coenzyme-B12-independent enzyme. We show that glycerol dehydration in the presence of the coenzyme-B12-dependent enzyme proceeds via a 1, 2-OH shift, which benefits from a significant catalytic reduction in the barrier. In contrast, the same reaction in the presence of the coenzyme-B12-independent enzyme is unlikely to involve the 1, 2-OH shift ; instead, a strong preference for direct loss of water from a radical intermediate is indicated. We show that this preference, and ultimately the evolution of such enzymes, is strongly linked with the reactivities of the species responsible for abstracting a hydrogen atom from the substrate. It appears that the hydrogen-reabstraction step involving the product-related radical is fundamental to the mechanistic preference. The unconventional 1, 2-OH shift seems to be required to generate a product-related radical of sufficient reactivity to cleave the relatively inactive C–H bond arising from the B12 cofactor. In the absence of B12, it is the relatively weak S–H bond of a cysteine residue that must be homolyzed. Such a transformation is much less demanding, and its inclusion apparently enables a simpler overall dehydration mechanism.

Izvorni jezik

Znanstvena područja


Projekt / tema
HRZZ-IP-2013-11-8238 - Računalna rješenja u bioznanostima: Značaj savitljivosti molekula (David Smith, )

Institut "Ruđer Bošković", Zagreb

Časopis indeksira:

  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • Arts & Humanities Citation Index (A&HCI)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus