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Int. J. Mol. Sci. 2018, 19(6), 1617; https://doi.org/10.3390/ijms19061617

Ligand Access Channels in Cytochrome P450 Enzymes: A Review

Laboratoire d’Ingénierie des Systèmes Biologiques et des Procédés, Université de Toulouse, CNRS, INRA, INSA, 31000 Toulouse, France
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Received: 18 April 2018 / Revised: 27 May 2018 / Accepted: 28 May 2018 / Published: 30 May 2018
(This article belongs to the Special Issue Cytochromes P450: Drug Metabolism and Bioactivation)
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Abstract

Quantitative structure-activity relationships may bring invaluable information on structural elements of both enzymes and substrates that, together, govern substrate specificity. Buried active sites in cytochrome P450 enzymes are connected to the solvent by a network of channels exiting at the distal surface of the protein. This review presents different in silico tools that were developed to uncover such channels in P450 crystal structures. It also lists some of the experimental evidence that actually suggest that these predicted channels might indeed play a critical role in modulating P450 functions. Amino acid residues at the entrance of the channels may participate to a first global ligand recognition of ligands by P450 enzymes before they reach the buried active site. Moreover, different P450 enzymes show different networks of predicted channels. The plasticity of P450 structures is also important to take into account when looking at how channels might play their role. View Full-Text
Keywords: P450; QSAR; channel; polycyclic; substrate specificity; CAVER; Computing Cavities, Channels, Pores and Pockets (CCCPP); Random acceleration molecular dynamics (RAMD); haloalkane dehalogenase; structure P450; QSAR; channel; polycyclic; substrate specificity; CAVER; Computing Cavities, Channels, Pores and Pockets (CCCPP); Random acceleration molecular dynamics (RAMD); haloalkane dehalogenase; structure
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Urban, P.; Lautier, T.; Pompon, D.; Truan, G. Ligand Access Channels in Cytochrome P450 Enzymes: A Review. Int. J. Mol. Sci. 2018, 19, 1617.

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