Butelase 1 is an Asx-specific ligase enabling peptide macrocyclization and synthesis
Proteases are ubiquitous in nature, whereas naturally occurring peptide ligases, enzymes catalyzing the reverse reactions of proteases, are rare occurrences. Here we describe the discovery of butelase 1, to our knowledge the first asparagine/aspartate (Asx) peptide ligase to be reported. This highly...
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| Format: | Journal Article |
| Sprache: | English |
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2015
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| Online Zugang: | https://hdl.handle.net/10356/79260 http://hdl.handle.net/10220/38787 |
| _version_ | 1826127413665333248 |
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| author | Qiu, Yibo Lian, Yilong Hemu, Xinya Wang, Shujing Nguyen, Giang Kien Truc Tam, James Pingkwan |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Qiu, Yibo Lian, Yilong Hemu, Xinya Wang, Shujing Nguyen, Giang Kien Truc Tam, James Pingkwan |
| author_sort | Qiu, Yibo |
| collection | NTU |
| description | Proteases are ubiquitous in nature, whereas naturally occurring peptide ligases, enzymes catalyzing the reverse reactions of proteases, are rare occurrences. Here we describe the discovery of butelase 1, to our knowledge the first asparagine/aspartate (Asx) peptide ligase to be reported. This highly efficient enzyme was isolated from Clitoria ternatea, a cyclic peptide-producing medicinal plant. Butelase 1 shares 71% sequence identity and the same catalytic triad with legumain proteases but does not hydrolyze the protease substrate of legumain. Instead, butelase 1 cyclizes various peptides of plant and animal origin with yields greater than 95%. With Kcat values of up to 17 s(-1) and catalytic efficiencies as high as 542,000 M(-1) s(-1), butelase 1 is the fastest peptide ligase known. Notably, butelase 1 also displays broad specificity for the N-terminal amino acids of the peptide substrate, thus providing a new tool for C terminus-specific intermolecular peptide ligations. |
| first_indexed | 2024-10-01T07:08:29Z |
| format | Journal Article |
| id | ntu-10356/79260 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:08:29Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/792602023-02-28T16:58:16Z Butelase 1 is an Asx-specific ligase enabling peptide macrocyclization and synthesis Qiu, Yibo Lian, Yilong Hemu, Xinya Wang, Shujing Nguyen, Giang Kien Truc Tam, James Pingkwan School of Biological Sciences Proteases are ubiquitous in nature, whereas naturally occurring peptide ligases, enzymes catalyzing the reverse reactions of proteases, are rare occurrences. Here we describe the discovery of butelase 1, to our knowledge the first asparagine/aspartate (Asx) peptide ligase to be reported. This highly efficient enzyme was isolated from Clitoria ternatea, a cyclic peptide-producing medicinal plant. Butelase 1 shares 71% sequence identity and the same catalytic triad with legumain proteases but does not hydrolyze the protease substrate of legumain. Instead, butelase 1 cyclizes various peptides of plant and animal origin with yields greater than 95%. With Kcat values of up to 17 s(-1) and catalytic efficiencies as high as 542,000 M(-1) s(-1), butelase 1 is the fastest peptide ligase known. Notably, butelase 1 also displays broad specificity for the N-terminal amino acids of the peptide substrate, thus providing a new tool for C terminus-specific intermolecular peptide ligations. Accepted version 2015-10-12T03:11:51Z 2019-12-06T13:21:03Z 2015-10-12T03:11:51Z 2019-12-06T13:21:03Z 2014 2014 Journal Article Nguyen, G. K. T., Wang, S., Qiu, Y., Hemu, X., Lian, Y., & Tam, J. P. (2014). Butelase 1 is an Asx-specific ligase enabling peptide macrocyclization and synthesis. Nature Chemical Biology, 10(9), 732-738. https://hdl.handle.net/10356/79260 http://hdl.handle.net/10220/38787 10.1038/nchembio.1586 en Nature Chemical Biology © 2014 Nature America, Inc. This is the author created version of a work that has been peer reviewed and accepted for publication by Nature Chemical Biology, Nature America, Inc. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1038/nchembio.1586]. application/pdf |
| spellingShingle | Qiu, Yibo Lian, Yilong Hemu, Xinya Wang, Shujing Nguyen, Giang Kien Truc Tam, James Pingkwan Butelase 1 is an Asx-specific ligase enabling peptide macrocyclization and synthesis |
| title | Butelase 1 is an Asx-specific ligase enabling peptide macrocyclization and synthesis |
| title_full | Butelase 1 is an Asx-specific ligase enabling peptide macrocyclization and synthesis |
| title_fullStr | Butelase 1 is an Asx-specific ligase enabling peptide macrocyclization and synthesis |
| title_full_unstemmed | Butelase 1 is an Asx-specific ligase enabling peptide macrocyclization and synthesis |
| title_short | Butelase 1 is an Asx-specific ligase enabling peptide macrocyclization and synthesis |
| title_sort | butelase 1 is an asx specific ligase enabling peptide macrocyclization and synthesis |
| url | https://hdl.handle.net/10356/79260 http://hdl.handle.net/10220/38787 |
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