A modern mode of activation for nucleic acid enzymes
Through evolution, enzymes have developed subtle modes of activation in order to ensure the sufficiently high substrate specificity required by modern cellular metabolism. One of these modes is the use of a target-dependent module (i.e. a docking domain) such as those found in signalling kinases. Up...
Đã lưu trong:
| Tác giả chính: | , , |
|---|---|
| Định dạng: | Other |
| Ngôn ngữ: | English |
| Năm xuất bản: |
Public Library of Science (PLoS)
2018
|
| Chủ đề: | |
| Truy cập Trực tuyến: | http://lrc.quangbinhuni.edu.vn:8181/dspace/handle/DHQB_123456789/3845 |
| Tags: |
Thêm thẻ
Không có thẻ, Hãy là người đầu tiên gắn thẻ bản ghi này!
|
| id |
oai:localhost:DHQB_123456789-3845 |
|---|---|
| recordtype |
dspace |
| spelling |
oai:localhost:DHQB_123456789-38452018-10-22T08:44:14Z A modern mode of activation for nucleic acid enzymes Dominique, Lévesque Francis, P Brière Jean-Pierre, Perreault Medicine Science Through evolution, enzymes have developed subtle modes of activation in order to ensure the sufficiently high substrate specificity required by modern cellular metabolism. One of these modes is the use of a target-dependent module (i.e. a docking domain) such as those found in signalling kinases. Upon the binding of the target to a docking domain, the substrate is positioned within the catalytic site. The prodomain acts as a target-dependent module switching the kinase from an off state to an on state. As compared to the allosteric mode of activation, there is no need for the presence of a third partner. None of the ribozymes discovered to date have such a mode of activation, nor does any other known RNA. Starting from a specific on/off adaptor for the hepatitis delta virus ribozyme, that differs but has a mechanism reminiscent of this signalling kinase, we have adapted this mode of activation, using the techniques of molecular engineering, to both catalytic RNAs and DNAs exhibiting various activities. Specifically, we adapted three cleaving ribozymes (hepatitis delta virus, hammerhead and hairpin ribozymes), a cleaving 10-23 deoxyribozyme, a ligating hairpin ribozyme and an artificially selected capping ribozyme. In each case, there was a significant gain in terms of substrate specificity. Even if this mode of control is unreported for natural catalytic nucleic acids, its use needs not be limited to proteinous enzymes. We suggest that the complexity of the modern cellular metabolism might have been an important selective pressure in this evolutionary process. 2018-08-23T08:01:16Z 2018-08-23T08:01:16Z 2007-07 Other 1932-6203 (Online) http://lrc.quangbinhuni.edu.vn:8181/dspace/handle/DHQB_123456789/3845 en Public Library of Science (PLoS) |
| institution |
Trung tâm Học liệu Đại học Quảng Bình (Dspace) |
| collection |
Trung tâm Học liệu Đại học Quảng Bình (Dspace) |
| language |
English |
| topic |
Medicine Science |
| spellingShingle |
Medicine Science Dominique, Lévesque Francis, P Brière Jean-Pierre, Perreault A modern mode of activation for nucleic acid enzymes |
| description |
Through evolution, enzymes have developed subtle modes of activation in order to ensure the sufficiently high substrate specificity required by modern cellular metabolism. One of these modes is the use of a target-dependent module (i.e. a docking domain) such as those found in signalling kinases. Upon the binding of the target to a docking domain, the substrate is positioned within the catalytic site. The prodomain acts as a target-dependent module switching the kinase from an off state to an on state. As compared to the allosteric mode of activation, there is no need for the presence of a third partner. None of the ribozymes discovered to date have such a mode of activation, nor does any other known RNA. Starting from a specific on/off adaptor for the hepatitis delta virus ribozyme, that differs but has a mechanism reminiscent of this signalling kinase, we have adapted this mode of activation, using the techniques of molecular engineering, to both catalytic RNAs and DNAs exhibiting various activities. Specifically, we adapted three cleaving ribozymes (hepatitis delta virus, hammerhead and hairpin ribozymes), a cleaving 10-23 deoxyribozyme, a ligating hairpin ribozyme and an artificially selected capping ribozyme. In each case, there was a significant gain in terms of substrate specificity. Even if this mode of control is unreported for natural catalytic nucleic acids, its use needs not be limited to proteinous enzymes. We suggest that the complexity of the modern cellular metabolism might have been an important selective pressure in this evolutionary process. |
| format |
Other |
| author |
Dominique, Lévesque Francis, P Brière Jean-Pierre, Perreault |
| author_facet |
Dominique, Lévesque Francis, P Brière Jean-Pierre, Perreault |
| author_sort |
Dominique, Lévesque |
| title |
A modern mode of activation for nucleic acid enzymes |
| title_short |
A modern mode of activation for nucleic acid enzymes |
| title_full |
A modern mode of activation for nucleic acid enzymes |
| title_fullStr |
A modern mode of activation for nucleic acid enzymes |
| title_full_unstemmed |
A modern mode of activation for nucleic acid enzymes |
| title_sort |
modern mode of activation for nucleic acid enzymes |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2018 |
| url |
http://lrc.quangbinhuni.edu.vn:8181/dspace/handle/DHQB_123456789/3845 |
| _version_ |
1717292450578432000 |
| score |
9,463379 |