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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.


The representative networks of the FDs show more detailed subgroupings. A and B are the same networks generated from the FDs cluster in Fig. 2 at a higher stringency, LogE < − 56. Eight major clusters (clusters with more than 50 member sequences in each) formed. The nodes are coloured by organism kingdom information (A) or their substrate specificities (B).
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f0015: The representative networks of the FDs show more detailed subgroupings. A and B are the same networks generated from the FDs cluster in Fig. 2 at a higher stringency, LogE < − 56. Eight major clusters (clusters with more than 50 member sequences in each) formed. The nodes are coloured by organism kingdom information (A) or their substrate specificities (B).

Mentions: The three main families within the membrane FAD superfamily (FD, ME, FE) can be further resolved by reducing the LogE filter to remove weak associations. The FD family contains the structurally characterized mammalian Δ9 stearoyl-CoA desaturases (SCD1s) [41], which share approximately 32% amino acid identity with other members of the FD subfamily. They are responsible for introducing the first CC bond into a saturated hydrocarbon chain [21]. At a logE value of − 56, eight major clusters are formed (Fig. 3). The largest cluster consists of acyl-CoA specific Δ9 FDs (FD-A). The only other cluster that contains experimentally characterized desaturases is the FD-C cluster, which contain the characterized bi-functional acyl-lipid-specific Arabidopsis thaliana Δ7/Δ9 desaturases (ADS1) [8].


Classification and substrate head-group specificity of membrane fatty acid desaturases
The representative networks of the FDs show more detailed subgroupings. A and B are the same networks generated from the FDs cluster in Fig. 2 at a higher stringency, LogE < − 56. Eight major clusters (clusters with more than 50 member sequences in each) formed. The nodes are coloured by organism kingdom information (A) or their substrate specificities (B).
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

f0015: The representative networks of the FDs show more detailed subgroupings. A and B are the same networks generated from the FDs cluster in Fig. 2 at a higher stringency, LogE < − 56. Eight major clusters (clusters with more than 50 member sequences in each) formed. The nodes are coloured by organism kingdom information (A) or their substrate specificities (B).
Mentions: The three main families within the membrane FAD superfamily (FD, ME, FE) can be further resolved by reducing the LogE filter to remove weak associations. The FD family contains the structurally characterized mammalian Δ9 stearoyl-CoA desaturases (SCD1s) [41], which share approximately 32% amino acid identity with other members of the FD subfamily. They are responsible for introducing the first CC bond into a saturated hydrocarbon chain [21]. At a logE value of − 56, eight major clusters are formed (Fig. 3). The largest cluster consists of acyl-CoA specific Δ9 FDs (FD-A). The only other cluster that contains experimentally characterized desaturases is the FD-C cluster, which contain the characterized bi-functional acyl-lipid-specific Arabidopsis thaliana Δ7/Δ9 desaturases (ADS1) [8].

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.