Proietti, G;
Abelak, KK;
Bishop-Bailey, D;
Macchiarulo, A;
Nobeli, I;
(2016)
Computational modelling of the binding of arachidonic acid to the human monooxygenase CYP2J2.
Journal of Molecular Modeling
, 22
(11)
, Article 279. 10.1007/s00894-016-3134-6.
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Abstract
An experimentally determined structure for human CYP2J2—a member of the cytochrome P450 family with significant and diverse roles across a number of tissues—does not yet exist. Our understanding of how CYP2J2 accommodates its cognate substrates and how it might be inhibited by other ligands thus relies on our ability to computationally predict such interactions using modelling techniques. In this study we present a computational investigation of the binding of arachidonic acid (AA) to CYP2J2 using homology modelling, induced fit docking (IFD) and molecular dynamics (MD) simulations. Our study reveals a catalytically competent binding mode for AA that is distinct from a recently published study that followed a different computational pipeline. Our proposed binding mode for AA is supported by crystal structures of complexes of related enzymes to inhibitors, and evolutionary conservation of a residue whose role appears essential for placing AA in the right site for catalysis.
| Type: | Article |
|---|---|
| Title: | Computational modelling of the binding of arachidonic acid to the human monooxygenase CYP2J2 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00894-016-3134-6 |
| Publisher version: | https://doi.org/10.1007/s00894-016-3134-6 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Technology, Biochemistry & Molecular Biology, Biophysics, Chemistry, Multidisciplinary, Computer Science, Interdisciplinary Applications, Chemistry, Computer Science, CYP2J2, Arachidonic acid, Homology model, Induced fit docking, Molecular dynamics, HUMAN CYTOCHROME-P450 2J2, MUTATION-INDUCED DYSFUNCTION, MOLECULAR-CLONING, CRYSTAL-STRUCTURE, METABOLISM, DISCOVERY, INHIBITORS, IDENTIFICATION, EXPRESSION, SUBSTRATE |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10073365 |
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