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Article

Four Major Channels Detected in the Cytochrome P450 3A4: A Step toward Understanding Its Multispecificity

1
Laboratoire de Biochimie Théorique, CNRS UPR 9080, Institut de Biologie Physico-Chimique, 75005 Paris, France
2
CEA/I2BC, CNRS UMR 9198, Université Paris Saclay, 91190 Gif-sur-Yvette, France
3
MTi, INSERM UMR-S 973, Université Paris Diderot, 75013 Paris, France
4
Unité de Recherche de Modélisation en Sciences Fondamentales et Didactique, BP244, Université de Tunis El Manar, 2092 Tunis, Tunisie
5
ITODYS, CNRS UMR 7086, Université Paris Diderot, 75013 Paris, France
6
E-pôle de Génoinformatique, CNRS UMR 7592, Institut Jacques Monod, 75013 Paris, France
*
Author to whom correspondence should be addressed.
Current address: CMPLI, INSERM U1133 (BFA, CNRS UMR 8251), Université Paris Diderot, 75013 Paris, France.
Int. J. Mol. Sci. 2019, 20(4), 987; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20040987
Received: 18 January 2019 / Revised: 12 February 2019 / Accepted: 20 February 2019 / Published: 25 February 2019
(This article belongs to the Special Issue Cytochromes P450: Drug Metabolism, Bioactivation and Biodiversity 2.0)
We computed the network of channels of the 3A4 isoform of the cytochrome P450 (CYP) on the basis of 16 crystal structures extracted from the Protein Data Bank (PDB). The calculations were performed with version 2 of the CCCPP software that we developed for this research project. We identified the minimal cost paths (MCPs) output by CCCPP as probable ways to access to the buried active site. The algorithm of calculation of the MCPs is presented in this paper, with its original method of visualization of the channels. We found that these MCPs constitute four major channels in CYP3A4. Among the many channels proposed by Cojocaru et al. in 2007, we found that only four of them open in 3A4. We provide a refined description of these channels together with associated quantitative data. View Full-Text
Keywords: cytochromes P450; CYP3A4; active site access channels; cavities boundaries; minimal cost paths cytochromes P450; CYP3A4; active site access channels; cavities boundaries; minimal cost paths
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MDPI and ACS Style

Benkaidali, L.; André, F.; Moroy, G.; Tangour, B.; Maurel, F.; Petitjean, M. Four Major Channels Detected in the Cytochrome P450 3A4: A Step toward Understanding Its Multispecificity. Int. J. Mol. Sci. 2019, 20, 987. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20040987

AMA Style

Benkaidali L, André F, Moroy G, Tangour B, Maurel F, Petitjean M. Four Major Channels Detected in the Cytochrome P450 3A4: A Step toward Understanding Its Multispecificity. International Journal of Molecular Sciences. 2019; 20(4):987. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20040987

Chicago/Turabian Style

Benkaidali, Lydia, François André, Gautier Moroy, Bahoueddine Tangour, François Maurel, and Michel Petitjean. 2019. "Four Major Channels Detected in the Cytochrome P450 3A4: A Step toward Understanding Its Multispecificity" International Journal of Molecular Sciences 20, no. 4: 987. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20040987

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