Three-dimensional models of the cytochromes P450 IA2, P450 IID6 and P450 IIIA4 were built by means of comparative modeling using the X-ray crystallographic structures of P450 CAM, P450 BM-3, P450 TERP and P450 ERYF as templates. The three cytochromes were analyzed both in their intrinsic structural features and in their interaction properties with fifty specific and non-specific substrates. Substrate/enzyme complexes were obtained by means of both automated rigid and flexible body docking. The comparative analysis of the three cytochromes and the selected substrates, in their free and bound forms, allowed for the building of semi-quantitative models of substrate specificity based on both molecular and intermolecular interaction descriptors. The results of this study provide new insights into the molecular determinants of substrate specificity for the three different eukaryotic P450 isozymes and constitute a useful tool for predicting the specificity of new compounds.

Theoretical investigation of substrate specificity for cytochromes p450 IA2, p450 IID6 and p450 IIIA4 / DE RIENZO, Francesca; Fanelli, Francesca; Menziani, Maria Cristina; DE BENEDETTI, Pier Giuseppe. - In: JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN. - ISSN 0920-654X. - ELETTRONICO. - 14:1(2000), pp. 93-116. [10.1023/A:1008187802746]

Theoretical investigation of substrate specificity for cytochromes p450 IA2, p450 IID6 and p450 IIIA4

DE RIENZO, Francesca;FANELLI, Francesca;MENZIANI, Maria Cristina;DE BENEDETTI, Pier Giuseppe
2000

Abstract

Three-dimensional models of the cytochromes P450 IA2, P450 IID6 and P450 IIIA4 were built by means of comparative modeling using the X-ray crystallographic structures of P450 CAM, P450 BM-3, P450 TERP and P450 ERYF as templates. The three cytochromes were analyzed both in their intrinsic structural features and in their interaction properties with fifty specific and non-specific substrates. Substrate/enzyme complexes were obtained by means of both automated rigid and flexible body docking. The comparative analysis of the three cytochromes and the selected substrates, in their free and bound forms, allowed for the building of semi-quantitative models of substrate specificity based on both molecular and intermolecular interaction descriptors. The results of this study provide new insights into the molecular determinants of substrate specificity for the three different eukaryotic P450 isozymes and constitute a useful tool for predicting the specificity of new compounds.
2000
14
1
93
116
Theoretical investigation of substrate specificity for cytochromes p450 IA2, p450 IID6 and p450 IIIA4 / DE RIENZO, Francesca; Fanelli, Francesca; Menziani, Maria Cristina; DE BENEDETTI, Pier Giuseppe. - In: JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN. - ISSN 0920-654X. - ELETTRONICO. - 14:1(2000), pp. 93-116. [10.1023/A:1008187802746]
DE RIENZO, Francesca; Fanelli, Francesca; Menziani, Maria Cristina; DE BENEDETTI, Pier Giuseppe
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/310683
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 71
  • ???jsp.display-item.citation.isi??? 68
social impact