Azole drugs trap cytochrome P450 EryK in alternative conformational states (Articolo in rivista)

Type
Label
  • Azole drugs trap cytochrome P450 EryK in alternative conformational states (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1021/bi101062v (literal)
Alternative label
  • Montemiglio LC; Gianni S; Vallone B; Savino C. (2010)
    Azole drugs trap cytochrome P450 EryK in alternative conformational states
    in Biochemistry (Easton); American Chemical Society, Washington (Stati Uniti d'America)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Montemiglio LC; Gianni S; Vallone B; Savino C. (literal)
Pagina inizio
  • 9199 (literal)
Pagina fine
  • 9206 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 49 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 8 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 43 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1. Univ Roma La Sapienza, Dept Biochem Sci, I-00185 Rome, Italy 2. CNR Inst Mol Biol & Pathol, I-00185 Rome, Italy (literal)
Titolo
  • Azole drugs trap cytochrome P450 EryK in alternative conformational states (literal)
Abstract
  • EryK is a bacterial cytochrome P450 that catalyzes the last hydroxylation occurring during the biosynthetic pathway of erythromycin A in Streptomyces erythraeus. We report the crystal structures of EryK in complex with two widely used azole inhibitors: ketoconazole and clotrimazole. Both of these ligands use their imidazole moiety to coordinate the heme iron of P450s. Nevertheless, because of the different chemical and structural properties of their N1-substituent group, ketoconazole and clotrimazole trap EryK, respectively, in a closed and in an open conformation that resemble the two structures previously described for the ligand-free EryK. Indeed, ligands induce a distortion of the internal helix I that affects the accessibility of the binding pocket by regulating the kink of the external helix G via a network of interactions that involves helix F. The data presented thus constitute an example of how a cytochrome P450 may be selectively trapped in different conformational states by inhibitors. (literal)
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