Docking simulation and antibiotic discovery targeting the MlaC protein in Gram-negative bacteria
| Autor: | Huang, Yu-Ming M, Munguia, Jason, Miao, Yinglong, Nizet, Victor, McCammon, J Andrew |
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| Rok vydání: | 2019 |
| Předmět: |
Protein Structure
Binding Sites drug design Medicinal & Biomolecular Chemistry Biophysics Membrane Transport Proteins virtual screening Anti-Bacterial Agents Molecular Docking Simulation Infectious Diseases Bacterial Proteins 5.1 Pharmaceuticals Generic Health Relevance antibiotic Gram-Negative Bacteria MlaC protein Biochemistry and Cell Biology Development of treatments and therapeutic interventions Novobiocin Phospholipids Tertiary |
| Zdroj: | Chemical biology & drug design, vol 93, iss 4 |
| Popis: | To maintain the lipid asymmetry of the cell envelope in Gram-negative bacteria, the MlaC protein serves as a lipid transfer factor and delivers phospholipids from the outer to the inner membrane. A strategy of antibiotic discovery is to design a proper compound that can tightly bind to the MlaC protein and inhibit the MlaC function. In this study, we performed virtual screening on multiple MlaC structures obtained from molecular dynamics simulations to identify potential MlaC binders. Our results suggested that clorobiocin is a compound that could bind to the MlaC protein. Through the comparison of the bound geometry between clorobiocin and novobiocin, we pointed out that the methyl-pyrrole group of the noviose sugar in clorobiocin forms hydrophobic interactions with amino acids in the phospholipid binding pocket, which allows the compound to bind deep in the active site. This also explains why clorobiocin shows a tighter binding affinity than novobiocin. Our study highlights a practical path of antibiotic development against Gram-negative bacteria. |
| Databáze: | OpenAIRE |
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