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Divergent mechanisms of suicide inactivation for ethanolamine ammonia-lyase

Sandala, Greg M.; Smith, David M.; Radom, Leo
Divergent mechanisms of suicide inactivation for ethanolamine ammonia-lyase // Journal of the American Chemical Society, 127 (2005), 8856-8864 (međunarodna recenzija, članak, znanstveni)

Divergent mechanisms of suicide inactivation for ethanolamine ammonia-lyase

Sandala, Greg M. ; Smith, David M. ; Radom, Leo

Journal of the American Chemical Society (0002-7863) 127 (2005); 8856-8864

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

Ključne riječi
Ab initio; coenzyme B12; suicide inactivation

Ab initio molecular orbital calculations have been used to study the mechanism of suicide inactivation of ethanolamine ammonia-lyase induced by three different substrate analogues. Analysis of the normal catalytic mechanism with 2-aminoethanol (ethanolamine) as substrate predicts that both the hydrogen-abstraction and hydrogen-reabstraction steps involving the B-12-cofactor are likely to be exothermic. On the other hand, the proposed inactivation mechanism for the first substrate analogue, glycolaldehyde, leads to a highly stabilized radical that results in a very endothermic (by ca. 90 kJ mol(-1)) hydrogenreabstraction step, which is thought to halt the normal function of the enzyme. Curiously, the energy requirements for a catalytically imposed mechanism in the case of the second substrate analogue, 2-hydroxyethylhydrazine (HEH), parallel those for the catalytic substrate, despite the fact that HEH is found to inactivate EAL experimentally. However, further analysis reveals the presence of a lower energy pathway for HEH that leads to the formation of the highly stabilized hydrazinium radical cation. In a manner similar to when glycolalclehyde is the substrate analogue, this results in an endothermicity for the hydrogenreabstraction step that is prohibitively large. In contrast to these related inactivation mechanisms, the third substrate analogue, 2-aminoacetaldehyde, apparently accomplishes the inactivation of EAL in an entirely different manner. A pathway for the experimentally observed formation of acetic acid and ammonium cation has been identified and appears catalytic in the sense that 5'-deoxyadenosyl radical is regenerated. However, mechanisms to account for the subsequent formation of 4', 5'-anhydroadenosine and degradation of the corrinoid ring of the cofactor have not been elucidated.

Izvorni jezik

Znanstvena područja
Fizika, Kemija, Biologija


Projekt / tema

Institut "Ruđer Bošković", Zagreb

Autor s matičnim brojem:
David Matthew Smith, (260506)

Časopis indeksira:

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

Uključenost u ostale bibliografske baze podataka:

  • Chemical Abstracts