Protonation state and substrate binding to B2 metallo-beta-lactamase CphA from Aeromonas hydrofila (Articolo in rivista)

Type
Label
  • Protonation state and substrate binding to B2 metallo-beta-lactamase CphA from Aeromonas hydrofila (Articolo in rivista) (literal)
Anno
  • 2007-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1002/prot.21476 (literal)
Alternative label
  • Simona F.; Magistrato A.; Vera D.M.A.; Garau G.; Vila A.J.; Carloni P. (2007)
    Protonation state and substrate binding to B2 metallo-beta-lactamase CphA from Aeromonas hydrofila
    in Proteins (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Simona F.; Magistrato A.; Vera D.M.A.; Garau G.; Vila A.J.; Carloni P. (literal)
Pagina inizio
  • 595 (literal)
Pagina fine
  • 605 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 69 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 3 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Scuola Int Super Studi Avanzati, I-34014 Trieste, Italy; CNR, INFM, Democritos Modeling Ctr Res Atomist Simulat, I-34014 Trieste, Italy; Univ Nacl Cordoba, Fac Ciencias, Dept Organ Chem, INFIQC, RA-5000 Cordoba, Argentina; Ist Sci San Raffaele, DIBIT, Biocrystallog Unit, I-20132 Milan, Italy; Univ Nacl Rosario, Fac Bioquim & Farmaceut, IBR, RA-2000 Rosario, Santa Fe, Argentina (literal)
Titolo
  • Protonation state and substrate binding to B2 metallo-beta-lactamase CphA from Aeromonas hydrofila (literal)
Abstract
  • The zinc enzymes metallo beta-lactamases counteract the beneficial action of beta-lactam antibiotics against bacterial infections, by hydrolyzing their beta-lactam rings. To understand structure/function relationships on a representative member of this class, the B2 M beta L CphA, we have investigated the H-bond pattern at the Zn enzymatic active site and substrate binding mode by molecular simulation methods. Extensive QM calculations at the DFT-BLYP level on eleven models of the protein active site, along with MD simulations of the protein in aqueous solution, allow us to propose two plausible protonation states for the unbound enzyme, which are probably in equilibrium. Docking procedures along with MD simulations and QM calculations suggest that in the complex between the enzyme and its substrate (biapenem), the latter is stable in only one of the two protonation states, in addition it exhibits two different binding modes, of which only one agrees with previous proposals. In both cases, the substrate is polarized as in aqueous solution. We conclude that addressing mechanistic issues on this class of enzymes requires a careful procedure to assign protonation states and substrate docking modes. (C) 2007 Wiley-Liss, Inc. (literal)
Prodotto di
Autore CNR
Insieme di parole chiave

Incoming links:


Autore CNR di
Prodotto
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
Insieme di parole chiave di
data.CNR.it