The NMR structure of the Orf63 lytic developmental protein from lambda bacteriophage
Abstract The orf63 gene resides in a region of the lambda bacteriophage genome between the exo and xis genes and is among the earliest genes transcribed during infection. In lambda phage and Shiga toxin (Stx) producing phages found in enterohemorrhagic Escherichia coli (EHEC) associated with food po...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-54508-9 |
| _version_ | 1797274738938085376 |
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| author | Naushaba Khan Tavawn Graham Katarzyna Franciszkiewicz Sylwia Bloch Bożena Nejman-Faleńczyk Alicja Wegrzyn Logan W. Donaldson |
| author_facet | Naushaba Khan Tavawn Graham Katarzyna Franciszkiewicz Sylwia Bloch Bożena Nejman-Faleńczyk Alicja Wegrzyn Logan W. Donaldson |
| author_sort | Naushaba Khan |
| collection | DOAJ |
| description | Abstract The orf63 gene resides in a region of the lambda bacteriophage genome between the exo and xis genes and is among the earliest genes transcribed during infection. In lambda phage and Shiga toxin (Stx) producing phages found in enterohemorrhagic Escherichia coli (EHEC) associated with food poisoning, Orf63 expression reduces the host survival and hastens the period between infection and lysis thereby giving it pro-lytic qualities. The NMR structure of dimeric Orf63 reveals a fold consisting of two helices and one strand that all make extensive intermolecular contacts. Structure-based data mining failed to identify any Orf63 homolog beyond the family of temperate bacteriophages. A machine learning approach was used to design an amphipathic helical ligand that bound a hydrophobic cleft on Orf63 with micromolar affinity. This approach may open a new path towards designing therapeutics that antagonize the contributions of Stx phages in EHEC outbreaks. |
| first_indexed | 2024-03-07T15:02:34Z |
| format | Article |
| id | doaj.art-a6a39165ca414dfd88922ee3c04d0461 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:02:34Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a6a39165ca414dfd88922ee3c04d04612024-03-05T19:03:13ZengNature PortfolioScientific Reports2045-23222024-02-011411910.1038/s41598-024-54508-9The NMR structure of the Orf63 lytic developmental protein from lambda bacteriophageNaushaba Khan0Tavawn Graham1Katarzyna Franciszkiewicz2Sylwia Bloch3Bożena Nejman-Faleńczyk4Alicja Wegrzyn5Logan W. Donaldson6Department of Biology, York UniversityDepartment of Biology, York UniversityDepartment of Molecular Biology, University of GdańskDepartment of Molecular Biology, University of GdańskDepartment of Molecular Biology, University of GdańskPhage Therapy Center, University Center for Applied and Interdisciplinary Research, University of GdańskDepartment of Biology, York UniversityAbstract The orf63 gene resides in a region of the lambda bacteriophage genome between the exo and xis genes and is among the earliest genes transcribed during infection. In lambda phage and Shiga toxin (Stx) producing phages found in enterohemorrhagic Escherichia coli (EHEC) associated with food poisoning, Orf63 expression reduces the host survival and hastens the period between infection and lysis thereby giving it pro-lytic qualities. The NMR structure of dimeric Orf63 reveals a fold consisting of two helices and one strand that all make extensive intermolecular contacts. Structure-based data mining failed to identify any Orf63 homolog beyond the family of temperate bacteriophages. A machine learning approach was used to design an amphipathic helical ligand that bound a hydrophobic cleft on Orf63 with micromolar affinity. This approach may open a new path towards designing therapeutics that antagonize the contributions of Stx phages in EHEC outbreaks.https://doi.org/10.1038/s41598-024-54508-9 |
| spellingShingle | Naushaba Khan Tavawn Graham Katarzyna Franciszkiewicz Sylwia Bloch Bożena Nejman-Faleńczyk Alicja Wegrzyn Logan W. Donaldson The NMR structure of the Orf63 lytic developmental protein from lambda bacteriophage Scientific Reports |
| title | The NMR structure of the Orf63 lytic developmental protein from lambda bacteriophage |
| title_full | The NMR structure of the Orf63 lytic developmental protein from lambda bacteriophage |
| title_fullStr | The NMR structure of the Orf63 lytic developmental protein from lambda bacteriophage |
| title_full_unstemmed | The NMR structure of the Orf63 lytic developmental protein from lambda bacteriophage |
| title_short | The NMR structure of the Orf63 lytic developmental protein from lambda bacteriophage |
| title_sort | nmr structure of the orf63 lytic developmental protein from lambda bacteriophage |
| url | https://doi.org/10.1038/s41598-024-54508-9 |
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