The crystal structure of P450-TT heme-domain provides the first structural insights into the versatile class VII P450s

Michele Tavanti; Joanne L. Porter; Colin W. Levy; J. Rubén Gómez Castellanos; Sabine L. Flitsch; Nicholas J. Turner

doi:10.1016/j.bbrc.2018.05.014

The crystal structure of P450-TT heme-domain provides the first structural insights into the versatile class VII P450s

Michele Tavanti, Joanne L. Porter, Colin W. Levy, J. Rubén Gómez Castellanos, Sabine L. Flitsch, Nicholas J. Turner^*

^*Corresponding author for this work

Universita Degli Studi di Pavia

Research output: Contribution to journal › Article › peer-review

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Abstract

The first crystal structure of a class VII P450, CYP116B46 from Tepidiphilus thermophilus, has been solved at 1.9 Å resolution. The structure reveals overall conservation of the P450-fold and a water conduit around the I-helix. Active site residues have been identified and sequence comparisons have been made with other class VII enzymes. A structure similarity search demonstrated that the P450-TT structure is similar to enzymes capable of oxy-functionalization of fatty acids, terpenes, macrolides, steroids and statins. The insight gained from solving this structure will provide a guideline for future engineering and modelling studies on this catalytically promiscuous class of enzymes.

Original language	English
Pages (from-to)	846-850
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	501
Issue number	4
Early online date	17 May 2018
DOIs	https://doi.org/10.1016/j.bbrc.2018.05.014
Publication status	Published - 17 May 2018

Keywords

Biocatalysis
C-H activation
Crystallography
CYP
Hydroxylation

Research Beacons, Institutes and Platforms

Manchester Institute of Biotechnology

Access to Document

10.1016/j.bbrc.2018.05.014

1-s2.0-S0006291X18310593-mainAccepted author manuscript, 989 KBLicence: CC BY-NC-ND

Cite this

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title = "The crystal structure of P450-TT heme-domain provides the first structural insights into the versatile class VII P450s",

abstract = "The first crystal structure of a class VII P450, CYP116B46 from Tepidiphilus thermophilus, has been solved at 1.9 {\AA} resolution. The structure reveals overall conservation of the P450-fold and a water conduit around the I-helix. Active site residues have been identified and sequence comparisons have been made with other class VII enzymes. A structure similarity search demonstrated that the P450-TT structure is similar to enzymes capable of oxy-functionalization of fatty acids, terpenes, macrolides, steroids and statins. The insight gained from solving this structure will provide a guideline for future engineering and modelling studies on this catalytically promiscuous class of enzymes.",

keywords = "Biocatalysis, C-H activation, Crystallography, CYP, Hydroxylation",

author = "Michele Tavanti and Porter, {Joanne L.} and Levy, {Colin W.} and {G{\'o}mez Castellanos}, {J. Rub{\'e}n} and Flitsch, {Sabine L.} and Turner, {Nicholas J.}",

year = "2018",

month = may,

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doi = "10.1016/j.bbrc.2018.05.014",

language = "English",

volume = "501",

pages = "846--850",

journal = "Biochemical and Biophysical Research Communications",

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T1 - The crystal structure of P450-TT heme-domain provides the first structural insights into the versatile class VII P450s

AU - Tavanti, Michele

AU - Porter, Joanne L.

AU - Levy, Colin W.

AU - Gómez Castellanos, J. Rubén

AU - Flitsch, Sabine L.

AU - Turner, Nicholas J.

PY - 2018/5/17

Y1 - 2018/5/17

N2 - The first crystal structure of a class VII P450, CYP116B46 from Tepidiphilus thermophilus, has been solved at 1.9 Å resolution. The structure reveals overall conservation of the P450-fold and a water conduit around the I-helix. Active site residues have been identified and sequence comparisons have been made with other class VII enzymes. A structure similarity search demonstrated that the P450-TT structure is similar to enzymes capable of oxy-functionalization of fatty acids, terpenes, macrolides, steroids and statins. The insight gained from solving this structure will provide a guideline for future engineering and modelling studies on this catalytically promiscuous class of enzymes.

AB - The first crystal structure of a class VII P450, CYP116B46 from Tepidiphilus thermophilus, has been solved at 1.9 Å resolution. The structure reveals overall conservation of the P450-fold and a water conduit around the I-helix. Active site residues have been identified and sequence comparisons have been made with other class VII enzymes. A structure similarity search demonstrated that the P450-TT structure is similar to enzymes capable of oxy-functionalization of fatty acids, terpenes, macrolides, steroids and statins. The insight gained from solving this structure will provide a guideline for future engineering and modelling studies on this catalytically promiscuous class of enzymes.

KW - Biocatalysis

KW - C-H activation

KW - Crystallography

KW - CYP

KW - Hydroxylation

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DO - 10.1016/j.bbrc.2018.05.014

M3 - Article

AN - SCOPUS:85047411916

SN - 0006-291X

VL - 501

SP - 846

EP - 850

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

The crystal structure of P450-TT heme-domain provides the first structural insights into the versatile class VII P450s

Abstract

Keywords

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Manchester Synthetic Biology Research Centre for Fine and Speciality Chemicals

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The crystal structure of P450-TT heme-domain provides the first structural insights into the versatile class VII P450s

Abstract

Keywords

Research Beacons, Institutes and Platforms

Access to Document

Other files and links

Fingerprint

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Manchester Synthetic Biology Research Centre for Fine and Speciality Chemicals

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