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Spectroscopy
Volume 25, Issue 2, Pages 63-87
http://dx.doi.org/10.3233/SPE-2011-0499

Modeling of cytochrome P450 (Cyt P450, CYP) channels

Christopher K. Jankowski,1,2,4,6 Julien B. Chiasson,1,3 Étienne Dako,1,4 Kathy Doucet,1,2 Marc E. Surette,1,2 Francois André,1,5 and Marcel Delaforge1,5

1Faculté des études supérieures et de la recherche, Université de Moncton, Moncton, NB, Canada
2Faculté des Sciences, Département de chimie et biochimie, Université de Moncton, Moncton, NB, Canada
3Département de l'informatique, Université de Moncton, Moncton, NB, Canada
4Faculté des sciences de la santé et des services communautaires, Université de Moncton, Moncton, NB, Canada
5Centre d9études nucléaires de Saclay, CEA, iBiTec-S/SB2SM, URA2096 CNRS, Gif-sur-Yvette, France
6Département de chimie et biochimie, Université de Moncton, Moncton, NB, E1A 3 E9, Canada

Copyright © 2011 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The precise location of a substrate in cytochrome P450 (CYP) governs the orientation of the oxidation position. Such information is generally obtained from biochemical data, but modeling approaches have also been used to explain these locations. We used X-ray data and modeling techniques to distinguish between the series of putative linear or curved channels which lead the substrate from the outer side of the protein to the inner, and then into the heme pocket; these techniques were also used to identify the largest such channels. Two new methods for precisely determining the 3-D structure of proteins using X-ray crystallography were proposed in order to identify these channels: first, the use of both straight and curved channels, and second, the sphere method. These data are compared with Poulos channels, and with Caver (or Mol on line) modeling methodologies. Our methods were developed from studies of the interaction between cytochrome P450CAM (CYP101) from Pseudomonas putida (as expressed in Escherichia coli) and the indolic base β-carboline. Apart from the identification of potential access channels leading to the heme-containing active site, a new explanation was advanced for the substrate's hydroxylation position. The sphere method seems to have potential to become a general and direct method for prediction of substrate access channels from reduced- or low-resolution crystallographic data.