Abstract
Coumermycin A1 is a natural aminocoumarin that inhibits bacterial DNA gyrase, a member of the GHKL proteins superfamily. We report here the first cocrystal structures of gyrase B bound to coumermycin A1, revealing that one coumermycin A1 molecule traps simultaneously two ATP-binding sites. The inhibited dimers from different species adopt distinct sequence-dependent conformations, alternative to the ATP-bound form. These structures provide a basis for the rational development of coumermycin A1 derivatives for antibiotherapy and biotechnology applications.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / chemistry
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Adenosine Triphosphate / metabolism
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Aminocoumarins / chemistry*
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Aminocoumarins / metabolism
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Binding Sites
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DNA Gyrase / chemistry*
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DNA Gyrase / metabolism
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Dimerization
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Escherichia coli / enzymology
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Hydrogen Bonding
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Molecular Dynamics Simulation
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Protein Structure, Quaternary
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Protein Subunits / chemistry
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Protein Subunits / metabolism
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Thermus thermophilus / enzymology
Substances
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Aminocoumarins
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Protein Subunits
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Adenosine Triphosphate
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DNA Gyrase
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coumermycin