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Evolution of substrate recognition sites (SRSs) in cytochromes P450 from Apiaceae exemplified by the CYP71AJ subfamily.

Dueholm B, Krieger C, Drew D, Olry A, Kamo T, Taboureau O, Weitzel C, Bourgaud F, Hehn A, Simonsen HT - BMC Evol. Biol. (2015)

Bottom Line: Large proliferations of cytochrome P450 encoding genes resulting from gene duplications can be termed as 'blooms', providing genetic material for the genesis and evolution of biosynthetic pathways.Homology models underline a significant modification of the accession to the iron atom, which might explain the difference of the substrate specificity between the cytochromes P450 restricted to furanocoumarins as substrates and the orphan CYP71AJ.The subclades show significant variability within their substrate recognition sites between the clades, suggesting different biochemical functions and providing insights into the evolution of cytochrome P450 'blooms' in response to environmental pressures.

View Article: PubMed Central - PubMed

Affiliation: University of Copenhagen, Department of Plant and Environmental Science, Copenhagen Plant Science Centre, Thorvaldsensvej 40, 1871, Frederiksberg C, Denmark. bjorn.dueholm@mymail.unisa.edu.au.

ABSTRACT

Background: Large proliferations of cytochrome P450 encoding genes resulting from gene duplications can be termed as 'blooms', providing genetic material for the genesis and evolution of biosynthetic pathways. Furanocoumarins are allelochemicals produced by many of the species in Apiaceaous plants belonging to the Apioideae subfamily of Apiaceae and have been described as being involved in the defence reaction against phytophageous insects.

Results: A bloom in the cytochromes P450 CYP71AJ subfamily has been identified, showing at least 2 clades and 6 subclades within the CYP71AJ subfamily. Two of the subclades were functionally assigned to the biosynthesis of furanocoumarins. Six substrate recognition sites (SRS1-6) important for the enzymatic conversion were investigated in the described cytochromes P450 and display significant variability within the CYP71AJ subfamily. Homology models underline a significant modification of the accession to the iron atom, which might explain the difference of the substrate specificity between the cytochromes P450 restricted to furanocoumarins as substrates and the orphan CYP71AJ.

Conclusion: Two subclades functionally assigned to the biosynthesis of furanocoumarins and four other subclades were identified and shown to be part of two distinct clades within the CYP71AJ subfamily. The subclades show significant variability within their substrate recognition sites between the clades, suggesting different biochemical functions and providing insights into the evolution of cytochrome P450 'blooms' in response to environmental pressures.

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SRS alignment of 19 cytochrome P450 belonging to the CYP71AJ subfamily. SRS means Substrate Recognition Site. The three-amino-acid motif is highlighted with a grey box. Residues likely to constitute the active site are indicated with triangles, and those in black are considered more reliable for their position in the homology models than those in grey
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Fig2: SRS alignment of 19 cytochrome P450 belonging to the CYP71AJ subfamily. SRS means Substrate Recognition Site. The three-amino-acid motif is highlighted with a grey box. Residues likely to constitute the active site are indicated with triangles, and those in black are considered more reliable for their position in the homology models than those in grey

Mentions: Despite low sequence similarity, the overall structure of cytochromes P450 is generally conserved and six substrate recognition sites (SRS1-6) have been identified to be necessary in the active site [17]. Thus, the SRS1-6 regions are very important for the binding and the subsequent enzymatic conversion of the substrate (Fig. 2) [18–20]. Other characteristic regions of plant and animal cytochrome P450s are the proline rich membrane hinge, the sequence surrounding the cysteine that is the axial ligand to the heme, the I-helix (i.e. SRS4) involved in oxygen binding, and the E-R-R triad using the Glu and Arg of the K-helix consensus (ExxR) and the Arg in the “PERF” consensus. The E-R-R triad is generally thought to be involved in locking the heme pocket into position and to ensure stabilization of the conserved core structure [17].Fig. 2


Evolution of substrate recognition sites (SRSs) in cytochromes P450 from Apiaceae exemplified by the CYP71AJ subfamily.

Dueholm B, Krieger C, Drew D, Olry A, Kamo T, Taboureau O, Weitzel C, Bourgaud F, Hehn A, Simonsen HT - BMC Evol. Biol. (2015)

SRS alignment of 19 cytochrome P450 belonging to the CYP71AJ subfamily. SRS means Substrate Recognition Site. The three-amino-acid motif is highlighted with a grey box. Residues likely to constitute the active site are indicated with triangles, and those in black are considered more reliable for their position in the homology models than those in grey
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4482195&req=5

Fig2: SRS alignment of 19 cytochrome P450 belonging to the CYP71AJ subfamily. SRS means Substrate Recognition Site. The three-amino-acid motif is highlighted with a grey box. Residues likely to constitute the active site are indicated with triangles, and those in black are considered more reliable for their position in the homology models than those in grey
Mentions: Despite low sequence similarity, the overall structure of cytochromes P450 is generally conserved and six substrate recognition sites (SRS1-6) have been identified to be necessary in the active site [17]. Thus, the SRS1-6 regions are very important for the binding and the subsequent enzymatic conversion of the substrate (Fig. 2) [18–20]. Other characteristic regions of plant and animal cytochrome P450s are the proline rich membrane hinge, the sequence surrounding the cysteine that is the axial ligand to the heme, the I-helix (i.e. SRS4) involved in oxygen binding, and the E-R-R triad using the Glu and Arg of the K-helix consensus (ExxR) and the Arg in the “PERF” consensus. The E-R-R triad is generally thought to be involved in locking the heme pocket into position and to ensure stabilization of the conserved core structure [17].Fig. 2

Bottom Line: Large proliferations of cytochrome P450 encoding genes resulting from gene duplications can be termed as 'blooms', providing genetic material for the genesis and evolution of biosynthetic pathways.Homology models underline a significant modification of the accession to the iron atom, which might explain the difference of the substrate specificity between the cytochromes P450 restricted to furanocoumarins as substrates and the orphan CYP71AJ.The subclades show significant variability within their substrate recognition sites between the clades, suggesting different biochemical functions and providing insights into the evolution of cytochrome P450 'blooms' in response to environmental pressures.

View Article: PubMed Central - PubMed

Affiliation: University of Copenhagen, Department of Plant and Environmental Science, Copenhagen Plant Science Centre, Thorvaldsensvej 40, 1871, Frederiksberg C, Denmark. bjorn.dueholm@mymail.unisa.edu.au.

ABSTRACT

Background: Large proliferations of cytochrome P450 encoding genes resulting from gene duplications can be termed as 'blooms', providing genetic material for the genesis and evolution of biosynthetic pathways. Furanocoumarins are allelochemicals produced by many of the species in Apiaceaous plants belonging to the Apioideae subfamily of Apiaceae and have been described as being involved in the defence reaction against phytophageous insects.

Results: A bloom in the cytochromes P450 CYP71AJ subfamily has been identified, showing at least 2 clades and 6 subclades within the CYP71AJ subfamily. Two of the subclades were functionally assigned to the biosynthesis of furanocoumarins. Six substrate recognition sites (SRS1-6) important for the enzymatic conversion were investigated in the described cytochromes P450 and display significant variability within the CYP71AJ subfamily. Homology models underline a significant modification of the accession to the iron atom, which might explain the difference of the substrate specificity between the cytochromes P450 restricted to furanocoumarins as substrates and the orphan CYP71AJ.

Conclusion: Two subclades functionally assigned to the biosynthesis of furanocoumarins and four other subclades were identified and shown to be part of two distinct clades within the CYP71AJ subfamily. The subclades show significant variability within their substrate recognition sites between the clades, suggesting different biochemical functions and providing insights into the evolution of cytochrome P450 'blooms' in response to environmental pressures.

Show MeSH