Abstract
In the last decades, the structural flexibility of cytochromes P450 has been extensively studied by spectroscopic and in silico methods. Here, both approaches are reviewed and compared. Comparison of both methods indicates that the individual cytochromes P450 differ significantly in the flexibilities of their substrate-binding active sites. This finding probably accounts for the large number of isoforms of these enzymes (there are fifty-seven known cytochrome P450 genes in the human genome) and their functional versatility. On the other hand, most of the known cytochrome P450s have a set of common structural features, with an overall structure consisting of a relatively flexible domain (the distal side), a more rigid domain (the heme-binding core) and a domain on the proximal side of the hemoprotein with intermediate flexibility. Substrate access and product egress channels of CYP enzymes are also important structural elements as the majority of these channels are located in the flexible distal side; the location, flexibility, and function of these channels are discussed.
Keywords: Cytochrome P450, flexibility, molecular dynamics, protein dynamics, substrate selectivity, growth regulators, xenobiotics, microsomal CYPs, channel flexibility, 3-hydroxyibuprofen
Current Drug Metabolism
Title: Is There a Relationship Between the Substrate Preferences and Structural Flexibility of Cytochromes P450?
Volume: 13 Issue: 2
Author(s): Michal Otyepka, Karel Berka and Pavel Anzenbacher
Affiliation:
Keywords: Cytochrome P450, flexibility, molecular dynamics, protein dynamics, substrate selectivity, growth regulators, xenobiotics, microsomal CYPs, channel flexibility, 3-hydroxyibuprofen
Abstract: In the last decades, the structural flexibility of cytochromes P450 has been extensively studied by spectroscopic and in silico methods. Here, both approaches are reviewed and compared. Comparison of both methods indicates that the individual cytochromes P450 differ significantly in the flexibilities of their substrate-binding active sites. This finding probably accounts for the large number of isoforms of these enzymes (there are fifty-seven known cytochrome P450 genes in the human genome) and their functional versatility. On the other hand, most of the known cytochrome P450s have a set of common structural features, with an overall structure consisting of a relatively flexible domain (the distal side), a more rigid domain (the heme-binding core) and a domain on the proximal side of the hemoprotein with intermediate flexibility. Substrate access and product egress channels of CYP enzymes are also important structural elements as the majority of these channels are located in the flexible distal side; the location, flexibility, and function of these channels are discussed.
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Cite this article as:
Otyepka Michal, Berka Karel and Anzenbacher Pavel, Is There a Relationship Between the Substrate Preferences and Structural Flexibility of Cytochromes P450?, Current Drug Metabolism 2012; 13 (2) . https://dx.doi.org/10.2174/138920012798918372
DOI https://dx.doi.org/10.2174/138920012798918372 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
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