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...
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| Main Authors: | , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
2021
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/146769 |
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| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | 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. |
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