A High‐Resolution Crystal Structure that Reveals Molecular Details of Target Recognition by the Calcium‐Dependent Lipopeptide Antibiotic Laspartomycin C

The calcium‐dependent antibiotics (CDAs) are an important emerging class of antibiotics. The crystal structure of the CDA laspartomycin C in complex with calcium and the ligand geranyl‐phosphate at a resolution of 1.28 Å is reported. This is the first crystal structure of a CDA bound to its bacteria...

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Bibliographic Details
Published in:Angewandte Chemie 2017-12, Vol.129 (52), p.16773-16776
Main Authors: Kleijn, Laurens H. J., Vlieg, Hedwich C., Wood, Thomas M., Sastre Toraño, Javier, Janssen, Bert J. C., Martin, Nathaniel I.
Format: Article
Language:English
Subjects:
Antibiotics
Bacteria
Bakterienzellwand
C55-P
Calcium
Calcium-abhängige Antibiotika
Chemistry
Crystal structure
Kristallstrukturen
Laspartomycin C
Molecular structure
Phospholipids
Target recognition
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Summary:The calcium‐dependent antibiotics (CDAs) are an important emerging class of antibiotics. The crystal structure of the CDA laspartomycin C in complex with calcium and the ligand geranyl‐phosphate at a resolution of 1.28 Å is reported. This is the first crystal structure of a CDA bound to its bacterial target. The structure is also the first to be reported for an antibiotic that binds the essential bacterial phospholipid undecaprenyl phosphate (C55‐P). These structural insights are of great value in the design of antibiotics capable of exploiting this unique bacterial target. Die Kristallstruktur des Calcium‐abhängigen Antibiotikums (CDA) Laspartomycin C im Komplex mit seinem bakteriellen Angriffsziel Undecaprenylphosphat (C55‐P) ist das erste Beispiel für einen entsprechenden Calcium enthaltenden CDA‐Komplex. Anders als klinisch eingesetzte Antibiotika tötet Laspartomycin C Bakterien, indem es an C55‐P bindet und die Peptidoglykan‐Biosynthese blockiert. Die vorgestellte Struktur illustriert diese Wechselwirkung.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201709240