Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/119813
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: The characterisation of two members of the cytochrome P450 CYP150 family: CYP150A5 and CYP150A6 from Mycobacterium marinum
Author: Child, S.
Flint, K.
Bruning, J.
Bell, S.
Citation: BBA - General Subjects, 2019; 1863(5):925-934
Publisher: Elsevier
Issue Date: 2019
ISSN: 0304-4165
1872-8006
Statement of
Responsibility: 
Stella A. Child, Kate L. Flint, John B. Bruning, Stephen G. Bell
Abstract: Background: Actinobacteria, including the Mycobacteria, have a large component of cytochrome P450 family monooxygenases. This includes Mycobacterium tuberculosis, M. ulcerans and M. marinum, and M. vanbaalenii. These enzymes can abstract CH bonds and have important roles in natural product biosynthesis. Methohds: Two members of the bacterial CYP150 family, CYP150A5 and CYP150A6 from M. marinum, were produced, purified and characterised. The potential substrate ranges of both enzymes were analysed and the monooxygenase activity of CYP150A5 was reconstituted using a physiological electron transfer partner system. CYP150A6 was structurally characterised by X-ray crystallography. Results: CYP150A5 was shown to bind various norisoprenoids and terpenoids. It could regioselectively hydroxylate β-ionol. The X-ray crystal structure of substrate-free CYP150A6 was solved to 1.5 Å. This displayed an open conformation with short F and G helices, an unresolved F-G loop region and exposed active site pocket. The active site residues could be identified and important variations were found among the CYP150A enzymes. Haem-binding azole inhibitors were identified for both enzymes. Conclusions: The structure of CYP150A6 will facilitate the identification of physiological substrates and the design of better inhibitors for members of this P450 family. Based on the observed differences in substrate binding preference and sequence variations among the active site residues, their roles are predicted to be different. General Significance: Multiple CYP150 family members were found in many bacteria and are prevalent in the Mycobacteria including several human pathogens. Inhibition and structural data are reported here for these enzymes for the first time.
Keywords: Biocatalysis; Cytochrome P450 monooxygenases; Mycobacterium; Enzyme inhibition; Ligand binding
Rights: © 2019 Elsevier B.V. All rights reserved.
RMID: 0030110412
DOI: 10.1016/j.bbagen.2019.02.016
Grant ID: http://purl.org/au-research/grants/arc/FT140100355
Appears in Collections:Biochemistry publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.