Insights into the Binding Mode of Lipid A to the Anti-lipopolysaccharide Factor ALFPm3 from Penaeus monodon: An In Silico Study through MD Simulations [Dataset]
The globally expanding threat of antibiotic resistance calls for the development of new strategies for abating Gram-negative bacterial infections. The use of extracorporeal blood cleansing devices with affinity sorbents to selectively capture bacterial lipopolysaccharide (LPS), which is the major co...
| Autores: | , , , , , , , |
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| Tipo de recurso: | conjunto de datos |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/361117 |
| Acceso en línea: | http://hdl.handle.net/10261/361117 |
| Access Level: | acceso abierto |
| Palabra clave: | Received outstanding interest Negative bacterial infections Globally expanding threat Extracorporeal blood detoxification Endotoxic principle ). Antibiotic resistance calls Alf isoform 3 Liipopolysaccharide factor alfpm3 “ al3 ” alfpm3 ), al3 within al3 residues Vitro validation Treating sepsis Specifically lys39 Silico study Silico predictions Significantly valuable Protein cavity Penaeus monodon Novel therapeutics New strategies Molecular dynamics Major constituent Hydrophobic interactions Derived results Binding pose Binding mode Bind tightly Also analyzed Aliphatic tails Affinity sorbents |
| Sumario: | The globally expanding threat of antibiotic resistance calls for the development of new strategies for abating Gram-negative bacterial infections. The use of extracorporeal blood cleansing devices with affinity sorbents to selectively capture bacterial lipopolysaccharide (LPS), which is the major constituent of Gram-negative bacterial outer membranes and the responsible agent for eliciting an exacerbated innate immune response in the host during infection, has received outstanding interest. For that purpose, molecules that bind tightly to LPS are required to functionalize the affinity sorbents. Particularly, anti-LPS factors (ALFs) are promising LPS-sequestrating molecules. Hence, in this work, molecular dynamics (MD) simulations are used to investigate the interaction mechanism and binding pose of the ALF isoform 3 from Penaeus monodon (ALFPm3), which is referred to as “AL3” for the sake of simplicity, and lipid A (LA, the component of LPS that represents its endotoxic principle). We concluded that hydrophobic interactions are responsible for AL3–LA binding and that LA binds to AL3 within the protein cavity, where it buries its aliphatic tails, whereas the negatively charged phosphate groups are exposed to the medium. AL3 residues that are key for its interaction with LA were identified, and their conservation in other ALFs (specifically Lys39 and Tyr49) was also analyzed. Additionally, based on the MD-derived results, we provide a picture of the possible AL3–LA interaction mechanism. Finally, an in vitro validation of the in silico predictions was performed. Overall, the insights gained from this work can guide the design of novel therapeutics for treating sepsis, since they may be significantly valuable for designing LPS-sequestrating molecules that could functionalize affinity sorbents to be used for extracorporeal blood detoxification. |
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