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Structure–Function Analysis of the Biotechnologically Important Cytochrome P450 107 (CYP107) Enzyme Family
,
David Lamb ,
David R. Nelson ,
Khajamohiddin Syed
Biomolecules, Volume: 13, Issue: 12, Start page: 1733
Swansea University Author:
David Lamb
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© 2023 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
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DOI (Published version): 10.3390/biom13121733
Abstract
Cytochrome P450 monooxygenases (CYPs) are a superfamily of heme-containing enzymes that are recognized for their vast substrate range and oxidative multifunctionality. CYP107 family members perform hydroxylation and epoxidation processes, producing a variety of biotechnologically useful secondary me...
| Published in: | Biomolecules |
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| ISSN: | 2218-273X |
| Published: |
MDPI AG
2023
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa66029 |
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| Abstract: |
Cytochrome P450 monooxygenases (CYPs) are a superfamily of heme-containing enzymes that are recognized for their vast substrate range and oxidative multifunctionality. CYP107 family members perform hydroxylation and epoxidation processes, producing a variety of biotechnologically useful secondary metabolites. Despite their biotechnological importance, a thorough examination of CYP107 protein structures regarding active site cavity dynamics and key amino acids interacting with bound ligands has yet to be undertaken. To address this research knowledge gap, 44 CYP107 crystal structures were investigated in this study. We demonstrate that the CYP107 active site cavity is very flexible, with ligand binding reducing the volume of the active site in some situations and increasing volume size in other instances. Polar interactions between the substrate and active site residues result in crucial salt bridges and the formation of proton shuttling pathways. Hydrophobic interactions, however, anchor the substrate within the active site. The amino acid residues within the binding pocket influence substrate orientation and anchoring, determining the position of the hydroxylation site and hence direct CYP107's catalytic activity. Additionally, the amino acid dynamics within and around the binding pocket determine CYP107's multifunctionality. This study serves as a reference for understanding the structure-function analysis of CYP107 family members precisely and the structure-function analysis of P450 enzymes in general. Finally, this work will aid in the genetic engineering of CYP107 enzymes to produce novel molecules of biotechnological interest. |
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| Keywords: |
CYP107; P450; active site; amino acid dynamics; crystal structure; enzymatic reaction; polar and hydrophobic interactions; secondary metabolites; substrate. |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
Khajamohiddin Syed expresses sincere gratitude to the University of Zululand (Grant number P419), and Tiara Padayachee thanks the National Research Foundation (NRF), South Africa, for postgraduate scholarships (grant number MND210504599108). |
| Issue: |
12 |
| Start Page: |
1733 |