The hydration of carbodiimide, isoelectronic with carbon dioxide, mediated by human carbonic anhydrase (EC 4.2.1.1) was studied at theoretical level in comparison with the native substrate. Quantum-mechanical (QM) and combined quantum-mechanics/molecular-mechanics (QM/MM) approaches indicate that human carbonic anhydrase is able to catalyze also the hydration of carbodiimide to urea with an energy barrier higher than that required by the native CO2. The ratedetermining step for both substrates is represented by the nucleophilic addition to the double bond, showing the final product ureate more strongly anchored to the enzyme active site than the hydrogen carbonate. The reduced catalytic activity for the carbodiimide substrate can be ascribed not only to the highest barrier but also to the difficulty in releasing the product in favor of the water molecule, delaying the catalytic turnover as indicated by QM and QM/MM analyses.

Promiscuous Ability of Human Carbonic Anhydrase: QM and QM/MM Investigation of Carbon Dioxide and Carbodiimide Hydration

MARINO, Tiziana;RUSSO, Nino
2014

Abstract

The hydration of carbodiimide, isoelectronic with carbon dioxide, mediated by human carbonic anhydrase (EC 4.2.1.1) was studied at theoretical level in comparison with the native substrate. Quantum-mechanical (QM) and combined quantum-mechanics/molecular-mechanics (QM/MM) approaches indicate that human carbonic anhydrase is able to catalyze also the hydration of carbodiimide to urea with an energy barrier higher than that required by the native CO2. The ratedetermining step for both substrates is represented by the nucleophilic addition to the double bond, showing the final product ureate more strongly anchored to the enzyme active site than the hydrogen carbonate. The reduced catalytic activity for the carbodiimide substrate can be ascribed not only to the highest barrier but also to the difficulty in releasing the product in favor of the water molecule, delaying the catalytic turnover as indicated by QM and QM/MM analyses.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11770/137389
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 22
social impact