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

Laurens H. J. Kleijn; Hedwich C. Vlieg; Thomas M. Wood; Javier Sastre Torano; Bert J. C. Janssen; Nathaniel I. Martin

doi:10.1002/anie.201709240

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

Laurens H. J. Kleijn
, Hedwich C. Vlieg
, Thomas M. Wood
, Javier Sastre Torano
, Bert J. C. Janssen^*
, Nathaniel I. Martin^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	16546-16549
Journal	Angewandte Chemie-International Edition
Volume	56
Issue number	52
DOIs	https://doi.org/10.1002/anie.201709240
Publication status	Published - 22 Dec 2017

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@article{898267dac3154b21932b406abc0319b8,

title = "A High-Resolution Crystal Structure that Reveals Molecular Details of Target Recognition by the Calcium-Dependent Lipopeptide Antibiotic Laspartomycin C",

abstract = "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 {\AA} 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.",

author = "Kleijn, \{Laurens H. J.\} and Vlieg, \{Hedwich C.\} and Wood, \{Thomas M.\} and \{Sastre Torano\}, Javier and Janssen, \{Bert J. C.\} and Martin, \{Nathaniel I.\}",

year = "2017",

month = dec,

day = "22",

doi = "10.1002/anie.201709240",

language = "English",

volume = "56",

pages = "16546--16549",

journal = "Angewandte Chemie-International Edition",

issn = "1433-7851",

publisher = "John Wiley and Sons Ltd",

number = "52",

}

A High-Resolution Crystal Structure that Reveals Molecular Details of Target Recognition by the Calcium-Dependent Lipopeptide Antibiotic Laspartomycin C. / Kleijn, Laurens H. J.; Vlieg, Hedwich C.; Wood, Thomas M. et al.
In: Angewandte Chemie-International Edition, Vol. 56, No. 52, 22.12.2017, p. 16546-16549.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - A High-Resolution Crystal Structure that Reveals Molecular Details of Target Recognition by the Calcium-Dependent Lipopeptide Antibiotic Laspartomycin C

AU - Kleijn, Laurens H. J.

AU - Vlieg, Hedwich C.

AU - Wood, Thomas M.

AU - Sastre Torano, Javier

AU - Janssen, Bert J. C.

AU - Martin, Nathaniel I.

PY - 2017/12/22

Y1 - 2017/12/22

N2 - 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.

AB - 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.

U2 - 10.1002/anie.201709240

DO - 10.1002/anie.201709240

M3 - Article

SN - 1433-7851

VL - 56

SP - 16546

EP - 16549

JO - Angewandte Chemie-International Edition

JF - Angewandte Chemie-International Edition

IS - 52

ER -

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

Abstract

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