X-ray absorption near-edge structure (XANES) spectroscopy and molecular dynamics (MD) simulations have been jointly applied to the study of the Cu,Zn superoxide dismutase from Haemophilus ducreyi (HdSOD) in interaction with the carbon monoxide molecule. The configurational flexibility of the Fe(II)-heme group, intercalated between the two subunits, has been sampled by MD simulations and included in the XANES data analysis without optimization in the structural parameter space. Our results provide an interpretation of the observed discrepancy in the Fe-heme distances as detected by extended X-ray absorption fine structure (EXAFS) spectroscopy and the classical XANES analysis, in which the structural parameters are optimized in a unique structure. Moreover, binding of the CO molecule to the heme induces a long range effect on the Cu,Zn active site, as evidenced by both MD simulations and in vitro experiments. MD simulation of the CO bound system, in fact, highlighted a structural rearrangement of the protein-protein hydrogen bond network in the region of the Cu,Zn active site, correlated with an increase in water accessibility at short distance from the copper atom. In line, in vitro experiments evidenced an increase of copper accessibility to a chelating agent when the CO molecule binds to the heme group, as compared to a heme deprived HdSOD. Altogether, our results support the hypothesis that the HdSOD is a heme-sensor protein, in which binding to small gaseous molecules modulates the enzyme superoxide activity as an adaptive response to the bacterial environment.

Chillemi, G., De Santis, S., Falconi, M., Mancini, G., Migliorati, V., Battistoni, A., et al. (2012). Carbon monoxide binding to the heme group at the dimeric interface modulates structure and copper accessibility in the Cu,Zn superoxide dismutase from Haemophilus ducreyi: in silico and in vitro evidences. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 30(3), 269-279 [10.1080/07391102.2012.680028].

Carbon monoxide binding to the heme group at the dimeric interface modulates structure and copper accessibility in the Cu,Zn superoxide dismutase from Haemophilus ducreyi: in silico and in vitro evidences.

Falconi M;Battistoni A;Pacello F;Desideri A;
2012-01-01

Abstract

X-ray absorption near-edge structure (XANES) spectroscopy and molecular dynamics (MD) simulations have been jointly applied to the study of the Cu,Zn superoxide dismutase from Haemophilus ducreyi (HdSOD) in interaction with the carbon monoxide molecule. The configurational flexibility of the Fe(II)-heme group, intercalated between the two subunits, has been sampled by MD simulations and included in the XANES data analysis without optimization in the structural parameter space. Our results provide an interpretation of the observed discrepancy in the Fe-heme distances as detected by extended X-ray absorption fine structure (EXAFS) spectroscopy and the classical XANES analysis, in which the structural parameters are optimized in a unique structure. Moreover, binding of the CO molecule to the heme induces a long range effect on the Cu,Zn active site, as evidenced by both MD simulations and in vitro experiments. MD simulation of the CO bound system, in fact, highlighted a structural rearrangement of the protein-protein hydrogen bond network in the region of the Cu,Zn active site, correlated with an increase in water accessibility at short distance from the copper atom. In line, in vitro experiments evidenced an increase of copper accessibility to a chelating agent when the CO molecule binds to the heme group, as compared to a heme deprived HdSOD. Altogether, our results support the hypothesis that the HdSOD is a heme-sensor protein, in which binding to small gaseous molecules modulates the enzyme superoxide activity as an adaptive response to the bacterial environment.
2012
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/11 - BIOLOGIA MOLECOLARE
English
Con Impact Factor ISI
Superoxide Dismutase; Heme; Models, Molecular; Catalytic Domain; Carbon Monoxide; Copper; Protein Binding; Hydrogen Bonding; Haemophilus ducreyi
http://www.tandfonline.com/doi/abs/10.1080/07391102.2012.680028?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed#.UjBBuuCzu0o
Chillemi, G., De Santis, S., Falconi, M., Mancini, G., Migliorati, V., Battistoni, A., et al. (2012). Carbon monoxide binding to the heme group at the dimeric interface modulates structure and copper accessibility in the Cu,Zn superoxide dismutase from Haemophilus ducreyi: in silico and in vitro evidences. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 30(3), 269-279 [10.1080/07391102.2012.680028].
Chillemi, G; De Santis, S; Falconi, M; Mancini, G; Migliorati, V; Battistoni, A; Pacello, F; Desideri, A; D’Angelo, P
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
78.Chillemi_JBSD_12.pdf

accesso aperto

Descrizione: Articolo principale
Dimensione 426.33 kB
Formato Adobe PDF
426.33 kB Adobe PDF Visualizza/Apri

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/2108/76802
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 4
social impact