De novo-designed β-sheet heme proteins
The field of de novo protein design has met with considerable success over the past few decades. Heme, a cofactor has often been introduced to impart a diverse array of functions to a protein, ranging from electron transport to respiration. In nature, heme is found to occur predominantly in α-helica...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2021
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| Online Access: | https://hdl.handle.net/10356/146769 |
| _version_ | 1824455156474839040 |
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| author | D'Souza, Areetha Bhattacharjya, Surajit |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences D'Souza, Areetha Bhattacharjya, Surajit |
| author_sort | D'Souza, Areetha |
| collection | NTU |
| description | The field of de novo protein design has met with considerable success over the past few decades. Heme, a cofactor has often been introduced to impart a diverse array of functions to a protein, ranging from electron transport to respiration. In nature, heme is found to occur predominantly in α-helical structures over β-sheets, which has resulted in significant designs of heme-proteins utilizing coiled coil helices. By contrast, there are only a few known β-sheet proteins that bind heme and designs of β-sheets frequently result in amyloid-like aggregates. This review reflects on our success with designing a series of multi-stranded β-sheet heme binding peptides that are well folded both in aqueous and membrane-like environments. Initially, we designed a β-hairpin peptide that self-assembles to bind heme and performs peroxidase activity in membrane. The β-hairpin was optimized further to accommodate a heme binding pocket within multi-stranded β-sheets for catalysis and electron transfer in membranes. Furthermore, we de novo designed and characterized β-sheet peptides and mini-proteins soluble in aqueous environment capable of binding single and multiple hemes with high affinity and stability. Collectively, these studies highlight substantial progress made towards the design of functional β-sheets. |
| first_indexed | 2025-02-19T03:33:44Z |
| format | Journal Article |
| id | ntu-10356/146769 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:33:44Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1467692023-02-28T17:08:31Z De novo-designed β-sheet heme proteins D'Souza, Areetha Bhattacharjya, Surajit School of Biological Sciences Science::Chemistry::Analytical chemistry::Proteins Protein Design Chemical Structures The field of de novo protein design has met with considerable success over the past few decades. Heme, a cofactor has often been introduced to impart a diverse array of functions to a protein, ranging from electron transport to respiration. In nature, heme is found to occur predominantly in α-helical structures over β-sheets, which has resulted in significant designs of heme-proteins utilizing coiled coil helices. By contrast, there are only a few known β-sheet proteins that bind heme and designs of β-sheets frequently result in amyloid-like aggregates. This review reflects on our success with designing a series of multi-stranded β-sheet heme binding peptides that are well folded both in aqueous and membrane-like environments. Initially, we designed a β-hairpin peptide that self-assembles to bind heme and performs peroxidase activity in membrane. The β-hairpin was optimized further to accommodate a heme binding pocket within multi-stranded β-sheets for catalysis and electron transfer in membranes. Furthermore, we de novo designed and characterized β-sheet peptides and mini-proteins soluble in aqueous environment capable of binding single and multiple hemes with high affinity and stability. Collectively, these studies highlight substantial progress made towards the design of functional β-sheets. Ministry of Education (MOE) Accepted version AS would like to thank Ministry of Education, Singapore and Nanyang Technological University for Graduate Research Scholarship. 2021-03-10T03:06:43Z 2021-03-10T03:06:43Z 2021 Journal Article D'Souza, A., & Bhattacharjya, S. (2021). De novo-designed β-sheet heme proteins. Biochemistry, 60(6), 431–439. doi:10.1021/acs.biochem.0c00662 0006-2960 https://hdl.handle.net/10356/146769 10.1021/acs.biochem.0c00662 6 60 431 439 en Biochemistry This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biochemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.biochem.0c00662 application/pdf |
| spellingShingle | Science::Chemistry::Analytical chemistry::Proteins Protein Design Chemical Structures D'Souza, Areetha Bhattacharjya, Surajit De novo-designed β-sheet heme proteins |
| title | De novo-designed β-sheet heme proteins |
| title_full | De novo-designed β-sheet heme proteins |
| title_fullStr | De novo-designed β-sheet heme proteins |
| title_full_unstemmed | De novo-designed β-sheet heme proteins |
| title_short | De novo-designed β-sheet heme proteins |
| title_sort | de novo designed β sheet heme proteins |
| topic | Science::Chemistry::Analytical chemistry::Proteins Protein Design Chemical Structures |
| url | https://hdl.handle.net/10356/146769 |
| work_keys_str_mv | AT dsouzaareetha denovodesignedbsheethemeproteins AT bhattacharjyasurajit denovodesignedbsheethemeproteins |