Conserved Structural Motif Identified in Peptides That Bind to Geminivirus Replication Protein Rep.
| dc.contributor.author | Ascencio-Ibáñez, J Trinidad | |
| dc.contributor.author | Bobay, Benjamin G | |
| dc.date.accessioned | 2023-09-01T14:26:07Z | |
| dc.date.available | 2023-09-01T14:26:07Z | |
| dc.date.issued | 2021-09 | |
| dc.date.updated | 2023-09-01T14:26:06Z | |
| dc.description.abstract | The geminivirus replication protein, Rep, has long been recognized as a high-value target for control of geminivirus infections as this protein is highly conserved and essential for viral replication and proliferation. In addition, inhibition of viral replication has been pursued through various antiviral strategies with varying degrees of success, including inhibitory peptides that target Rep. While much effort has centered around sequence characterization of the Rep protein and inhibitory peptides, detailed structural analysis has been missing. This study computationally investigated the presence of common structural features within these inhibitory peptides and if these features could inform if a particular peptide will bind Rep and/or interfere with viral replication. Molecular dynamics simulations of the inhibitory peptide library showed that simply possessing stable structural features does not inform interference of viral replication regardless of the binding of Rep. Additionally, nearly all known Rep inhibitory peptides sample a conserved β-sheet structural motif, possibly informing structure-function relationships in binding Rep. In particular, two peptides (A22 and A64) characterized by this structural motif were computationally docked against a wide variety of geminivirus Rep proteins to determine a mechanism of action. Computational docking revealed these peptides utilize a common Rep protein sequence motif for binding, HHN-x1/2-Q. The results identified residues in both Rep and the inhibitory peptides that play a significant role in the interaction, establishing the foundation for a rational structure-based design approach for the construction of both broadly reactive and geminivirus species-specific inhibitors. | |
| dc.identifier.issn | 0006-2960 | |
| dc.identifier.issn | 1520-4995 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | American Chemical Society (ACS) | |
| dc.relation.ispartof | Biochemistry | |
| dc.relation.isversionof | 10.1021/acs.biochem.1c00408 | |
| dc.subject | Geminiviridae | |
| dc.subject | DNA Helicases | |
| dc.subject | Peptides | |
| dc.subject | Viral Proteins | |
| dc.subject | DNA, Viral | |
| dc.subject | Virus Replication | |
| dc.subject | Amino Acid Sequence | |
| dc.subject | Amino Acid Motifs | |
| dc.subject | Protein Binding | |
| dc.title | Conserved Structural Motif Identified in Peptides That Bind to Geminivirus Replication Protein Rep. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Bobay, Benjamin G|0000-0003-4775-3686 | |
| pubs.begin-page | 2795 | |
| pubs.end-page | 2809 | |
| pubs.issue | 37 | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Radiology | |
| pubs.publication-status | Published | |
| pubs.volume | 60 |
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