The crystal structure of the d-alanine-d-alanine ligase from Acinetobacter baumannii suggests a flexible conformational change in the central domain before nucleotide binding

Kim Hung Huynh, Myoung ki Hong, Clarice Lee, Huyen Thi Tran, Sang Hee Lee, Yeh Jin Ahn, Sun Shin Cha, Lin Woo Kang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Acinetobacter baumannii, which is emerging as a multidrugresistant nosocomial pathogen, causes a number of diseases, including pneumonia, bacteremia, meningitis, and skin infections. With ATP hydrolysis, the D-alanine-D-alanine ligase (DDL) catalyzes the synthesis of D-alanyl-D-alanine, which is an essential component of bacterial peptidoglycan. In this study, we determined the crystal structure of DDL from A. baumannii (AbDDL) at a resolution of 2.2 Å. The asymmetric unit contained six protomers of AbDDL. Five protomers had a closed conformation in the central domain, while one protomer had an open conformation in the central domain. The central domain with an open conformation did not interact with crystallographic symmetry-related protomers and the conformational change of the central domain was not due to crystal packing. The central domain of AbDDL can have an ensemble of the open and closed conformations before the binding of substrate ATP. The conformational change of the central domain is important for the catalytic activity and the detail information will be useful for the development of inhibitors against AbDDL and putative antibacterial agents against A. baumannii. The AbDDL structure was compared with that of other DDLs that were in complex with potent inhibitors and the catalytic activity of AbDDL was confirmed using enzyme kinetics assays.

Original languageEnglish
Pages (from-to)776-782
Number of pages7
JournalJournal of Microbiology
Volume53
Issue number11
DOIs
StatePublished - 1 Nov 2015

Bibliographical note

Publisher Copyright:
© 2015, The Microbiological Society of Korea and Springer-Verlag Berlin Heidelberg.

Keywords

  • Acinetobacter baumannii
  • X-ray crystallography
  • bacterial cell wall synthesis
  • d-alanine-d-alanine ligase
  • drug target

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