Structure determinants for the substrate specificity of Acyl-CoA Δ9 desaturases from a marine copepod
In contrast to soluble acyl-ACP desaturases from plants, little is known about the structure-guiding principle underlying substrate specificity and regioselectivity of membrane-bound acyl-CoA desaturases from animals, mainly due to lack of the three-dimensional structure information. Here we report...
Published in: | ACS Chemical Biology |
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2014
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ftnrccanada:oai:cisti-icist.nrc-cnrc.ca:cistinparc:21272459 2023-05-15T15:48:07+02:00 Structure determinants for the substrate specificity of Acyl-CoA Δ9 desaturases from a marine copepod Meesapyodsuk, Dauenpen Qiu, Xiao 2014-04-18 text https://doi.org/10.1021/cb400675d https://nrc-publications.canada.ca/eng/view/object/?id=cdd0d360-444a-4c4a-8804-837b92ef05b4 https://nrc-publications.canada.ca/fra/voir/objet/?id=cdd0d360-444a-4c4a-8804-837b92ef05b4 eng eng issn:1554-8929 ACS Chemical Biology, Volume: 9, Issue: 4, Publication date: 2014-04-18, Pages: 922–934 doi:10.1021/cb400675d article 2014 ftnrccanada https://doi.org/10.1021/cb400675d 2021-09-01T06:28:15Z In contrast to soluble acyl-ACP desaturases from plants, little is known about the structure-guiding principle underlying substrate specificity and regioselectivity of membrane-bound acyl-CoA desaturases from animals, mainly due to lack of the three-dimensional structure information. Here we report identification of two homologous membrane-bound acyl-CoA Δ9 desaturases (ChDes9-1 and ChDes9-2) from the marine copepod Calanus hyperboreus that accumulates more than 90% of total storage lipids in the form of wax esters. ChDes9-2 is a common Δ9 desaturase with substrate specificity to long chain fatty acid 18:0, while ChDes9-1 is a new type of Δ9 desaturase introducing a Δ9 double bond into a wide range of very long chain fatty acids ranging from 20:0 to 26:0. Reciprocal domain swapping and site-directed mutagenesis guided by the membrane topology revealed that presence or absence of an amphipathic and bulky residue, tyrosine, in the middle of the second transmembrane domain was important in determining the substrate specificity of the two desaturases. To examine the mechanistic structure for the substrate specificity, tyrosine-scanning mutagenesis was employed to systematically substitute the residues in the transmembrane domain of the very long chain desaturase. The results showed that the transmembrane domain formed an α-helix structure probably involved in formation of the substrate-binding pocket and the corresponding residue of the tyrosine likely resided at the critical position within the pocket mediating the interaction with the substrates, thereby specifying the chain length of the substrates. Peer reviewed: Yes NRC publication: Yes Article in Journal/Newspaper Calanus hyperboreus National Research Council Canada: NRC Publications Archive ACS Chemical Biology 9 4 922 934 |
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Open Polar |
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National Research Council Canada: NRC Publications Archive |
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ftnrccanada |
language |
English |
description |
In contrast to soluble acyl-ACP desaturases from plants, little is known about the structure-guiding principle underlying substrate specificity and regioselectivity of membrane-bound acyl-CoA desaturases from animals, mainly due to lack of the three-dimensional structure information. Here we report identification of two homologous membrane-bound acyl-CoA Δ9 desaturases (ChDes9-1 and ChDes9-2) from the marine copepod Calanus hyperboreus that accumulates more than 90% of total storage lipids in the form of wax esters. ChDes9-2 is a common Δ9 desaturase with substrate specificity to long chain fatty acid 18:0, while ChDes9-1 is a new type of Δ9 desaturase introducing a Δ9 double bond into a wide range of very long chain fatty acids ranging from 20:0 to 26:0. Reciprocal domain swapping and site-directed mutagenesis guided by the membrane topology revealed that presence or absence of an amphipathic and bulky residue, tyrosine, in the middle of the second transmembrane domain was important in determining the substrate specificity of the two desaturases. To examine the mechanistic structure for the substrate specificity, tyrosine-scanning mutagenesis was employed to systematically substitute the residues in the transmembrane domain of the very long chain desaturase. The results showed that the transmembrane domain formed an α-helix structure probably involved in formation of the substrate-binding pocket and the corresponding residue of the tyrosine likely resided at the critical position within the pocket mediating the interaction with the substrates, thereby specifying the chain length of the substrates. Peer reviewed: Yes NRC publication: Yes |
format |
Article in Journal/Newspaper |
author |
Meesapyodsuk, Dauenpen Qiu, Xiao |
spellingShingle |
Meesapyodsuk, Dauenpen Qiu, Xiao Structure determinants for the substrate specificity of Acyl-CoA Δ9 desaturases from a marine copepod |
author_facet |
Meesapyodsuk, Dauenpen Qiu, Xiao |
author_sort |
Meesapyodsuk, Dauenpen |
title |
Structure determinants for the substrate specificity of Acyl-CoA Δ9 desaturases from a marine copepod |
title_short |
Structure determinants for the substrate specificity of Acyl-CoA Δ9 desaturases from a marine copepod |
title_full |
Structure determinants for the substrate specificity of Acyl-CoA Δ9 desaturases from a marine copepod |
title_fullStr |
Structure determinants for the substrate specificity of Acyl-CoA Δ9 desaturases from a marine copepod |
title_full_unstemmed |
Structure determinants for the substrate specificity of Acyl-CoA Δ9 desaturases from a marine copepod |
title_sort |
structure determinants for the substrate specificity of acyl-coa δ9 desaturases from a marine copepod |
publishDate |
2014 |
url |
https://doi.org/10.1021/cb400675d https://nrc-publications.canada.ca/eng/view/object/?id=cdd0d360-444a-4c4a-8804-837b92ef05b4 https://nrc-publications.canada.ca/fra/voir/objet/?id=cdd0d360-444a-4c4a-8804-837b92ef05b4 |
genre |
Calanus hyperboreus |
genre_facet |
Calanus hyperboreus |
op_relation |
issn:1554-8929 ACS Chemical Biology, Volume: 9, Issue: 4, Publication date: 2014-04-18, Pages: 922–934 doi:10.1021/cb400675d |
op_doi |
https://doi.org/10.1021/cb400675d |
container_title |
ACS Chemical Biology |
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9 |
container_issue |
4 |
container_start_page |
922 |
op_container_end_page |
934 |
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1766383117648527360 |