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Classification and substrate head-group specificity of membrane fatty acid desaturases

View Article: PubMed Central - PubMed

ABSTRACT

Membrane fatty acid desaturases are a diverse superfamily of enzymes that catalyze the introduction of double bonds into fatty acids. They are essential in a range of metabolic processes, such as the production of omega-3 fatty acids. However, our structure–function understanding of this superfamily is still developing and their range of activities and substrate specificities are broad, and often overlapping, which has made their systematic characterization challenging. A central issue with characterizing these proteins has been the lack of a structural model, which has been overcome with the recent publication of the crystal structures of two mammalian fatty acid desaturases. In this work, we have used sequence similarity networks to investigate the similarity among over 5000 related membrane fatty acid desaturase sequences, leading to a detailed classification of the superfamily, families and subfamilies with regard to their function and substrate head-group specificity. This work will facilitate rapid prediction of the function and specificity of new and existing sequences, as well as forming a basis for future efforts to manipulate the substrate specificity of these proteins for biotechnology applications.

No MeSH data available.


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Separation of the FE desaturase family into smaller groups. A and B are the same networks generated from the FEs cluster in Fig. 2 at a higher stringency, LogE < − 20. The nodes are coloured by organism kingdom information (A) and their substrate specificities reported in the literature (B).
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f0035: Separation of the FE desaturase family into smaller groups. A and B are the same networks generated from the FEs cluster in Fig. 2 at a higher stringency, LogE < − 20. The nodes are coloured by organism kingdom information (A) and their substrate specificities reported in the literature (B).

Mentions: The FE desaturases are responsible for introducing carbon–carbon double bonds into unsaturated acyl chains between the pre-existing double bonds and the carboxyl group of lipid substrates [52]. There is currently no crystal structure of any member of the FE desaturase family. Thus, our understanding of their mechanism and regioselectivity is primarily based on mutagenesis studies, which have been reviewed by Meesapyodsuk and Qiu [4]. A range of FEs with Δ4, Δ5, Δ6 desaturases activity and specificity for acyl-CoA or acyl-PC substrates have been identified [4], [20], [53], [54], [55], [56], [57]. This level of diversity is not seen in the other FAD families, making FE desaturases distinct from MEs and FDs. With a LogE < − 20 filter, the broad FE desaturase family separated into four clusters. For ease of explanation, the clades are named as FE1–4 (Fig. 7). The fusion-FADs, which have a cytochrome b5 domain fused at the N-terminus of the desaturase domain, are only found in the FE1–3 clusters.


Classification and substrate head-group specificity of membrane fatty acid desaturases
Separation of the FE desaturase family into smaller groups. A and B are the same networks generated from the FEs cluster in Fig. 2 at a higher stringency, LogE < − 20. The nodes are coloured by organism kingdom information (A) and their substrate specificities reported in the literature (B).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037126&req=5

f0035: Separation of the FE desaturase family into smaller groups. A and B are the same networks generated from the FEs cluster in Fig. 2 at a higher stringency, LogE < − 20. The nodes are coloured by organism kingdom information (A) and their substrate specificities reported in the literature (B).
Mentions: The FE desaturases are responsible for introducing carbon–carbon double bonds into unsaturated acyl chains between the pre-existing double bonds and the carboxyl group of lipid substrates [52]. There is currently no crystal structure of any member of the FE desaturase family. Thus, our understanding of their mechanism and regioselectivity is primarily based on mutagenesis studies, which have been reviewed by Meesapyodsuk and Qiu [4]. A range of FEs with Δ4, Δ5, Δ6 desaturases activity and specificity for acyl-CoA or acyl-PC substrates have been identified [4], [20], [53], [54], [55], [56], [57]. This level of diversity is not seen in the other FAD families, making FE desaturases distinct from MEs and FDs. With a LogE < − 20 filter, the broad FE desaturase family separated into four clusters. For ease of explanation, the clades are named as FE1–4 (Fig. 7). The fusion-FADs, which have a cytochrome b5 domain fused at the N-terminus of the desaturase domain, are only found in the FE1–3 clusters.

View Article: PubMed Central - PubMed

ABSTRACT

Membrane fatty acid desaturases are a diverse superfamily of enzymes that catalyze the introduction of double bonds into fatty acids. They are essential in a range of metabolic processes, such as the production of omega-3 fatty acids. However, our structure&ndash;function understanding of this superfamily is still developing and their range of activities and substrate specificities are broad, and often overlapping, which has made their systematic characterization challenging. A central issue with characterizing these proteins has been the lack of a structural model, which has been overcome with the recent publication of the crystal structures of two mammalian fatty acid desaturases. In this work, we have used sequence similarity networks to investigate the similarity among over 5000 related membrane fatty acid desaturase sequences, leading to a detailed classification of the superfamily, families and subfamilies with regard to their function and substrate head-group specificity. This work will facilitate rapid prediction of the function and specificity of new and existing sequences, as well as forming a basis for future efforts to manipulate the substrate specificity of these proteins for biotechnology applications.

No MeSH data available.


Related in: MedlinePlus