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The dimeric form of flavocytochrome P450 BM3 is catalytically functional as a fatty acid hydroxylase

The dimeric form of flavocytochrome P450 BM3 is catalytically functional as a fatty acid hydroxylase
The dimeric form of flavocytochrome P450 BM3 is catalytically functional as a fatty acid hydroxylase
In the model P450 BM3 system, the P450 is fused to its diflavin reductase partner in a single polypeptide. BM3 dimerizes in solution, but the catalytic relevance of the phenomenon was hitherto unknown. We show that BM3 fatty acid hydroxylase specific activity decreases sharply at low enzyme concentrations, consistent with separation of active dimer into inactive monomer. Reductase-dependent specific activities are maintained or enhanced at low concentration, suggesting inter-flavin electron transfer is unaffected. Fatty acid oxidation is reconstituted by mixing inactive oxygenase (A264H) and FMN-depleted (G570D) mutants, demonstrating that inter-monomer (FMN1-to-heme2) electron transfer supports oxygenase activity in the BM3 dimer.
0014-5793
5582-5588
Neeli, Rajasekhar
8569f8f4-1312-42b7-92dc-586144785eef
Girvan, Hazel M.
e2a78ec2-23e4-4726-b139-e67eb122036e
Lawrence, Andrew
ce503b40-0155-486f-bb1d-26830b61b5f1
Warren, Martin J.
3928fae6-cdea-4952-b453-0af7d2b17390
Leys, David
e05d7ef6-5e6b-4355-97ae-2e1be0ca3ef9
Scrutton, Nigel S.
9318ed79-a268-4f08-abbd-778aff36fe8d
Munro, Andrew W.
4b84bf85-fe62-4d34-8f0e-f5824af1126f
Neeli, Rajasekhar
8569f8f4-1312-42b7-92dc-586144785eef
Girvan, Hazel M.
e2a78ec2-23e4-4726-b139-e67eb122036e
Lawrence, Andrew
ce503b40-0155-486f-bb1d-26830b61b5f1
Warren, Martin J.
3928fae6-cdea-4952-b453-0af7d2b17390
Leys, David
e05d7ef6-5e6b-4355-97ae-2e1be0ca3ef9
Scrutton, Nigel S.
9318ed79-a268-4f08-abbd-778aff36fe8d
Munro, Andrew W.
4b84bf85-fe62-4d34-8f0e-f5824af1126f

Neeli, Rajasekhar, Girvan, Hazel M., Lawrence, Andrew, Warren, Martin J., Leys, David, Scrutton, Nigel S. and Munro, Andrew W. (2005) The dimeric form of flavocytochrome P450 BM3 is catalytically functional as a fatty acid hydroxylase. FEBS Letters, 579 (25), 5582-5588. (doi:10.1016/j.febslet.2005.09.023).

Record type: Article

Abstract

In the model P450 BM3 system, the P450 is fused to its diflavin reductase partner in a single polypeptide. BM3 dimerizes in solution, but the catalytic relevance of the phenomenon was hitherto unknown. We show that BM3 fatty acid hydroxylase specific activity decreases sharply at low enzyme concentrations, consistent with separation of active dimer into inactive monomer. Reductase-dependent specific activities are maintained or enhanced at low concentration, suggesting inter-flavin electron transfer is unaffected. Fatty acid oxidation is reconstituted by mixing inactive oxygenase (A264H) and FMN-depleted (G570D) mutants, demonstrating that inter-monomer (FMN1-to-heme2) electron transfer supports oxygenase activity in the BM3 dimer.

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More information

Accepted/In Press date: 12 September 2005
e-pub ahead of print date: 28 September 2005

Identifiers

Local EPrints ID: 488324
URI: http://eprints.soton.ac.uk/id/eprint/488324
ISSN: 0014-5793
PURE UUID: d4cc9c27-e4e4-4545-a86c-a8955709bc5d
ORCID for Andrew Lawrence: ORCID iD orcid.org/0000-0002-5853-5409

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Date deposited: 20 Mar 2024 17:48
Last modified: 21 Mar 2024 03:11

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Contributors

Author: Rajasekhar Neeli
Author: Hazel M. Girvan
Author: Andrew Lawrence ORCID iD
Author: Martin J. Warren
Author: David Leys
Author: Nigel S. Scrutton
Author: Andrew W. Munro

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