Journal of Microbiology

, Volume 53, Issue 11, pp 776–782 | Cite as

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
Microbial Physiology and Biochemistry
First Online:
Received:
Revised:
Accepted:

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.

Keywords

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

© The Microbiological Society of Korea and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Kim-Hung Huynh
    • 1
  • Myoung-ki Hong
    • 1
  • Clarice Lee
    • 1
    • 2
  • Huyen-Thi Tran
    • 1
  • Sang Hee Lee
    • 3
  • Yeh-Jin Ahn
    • 4
  • Sun-Shin Cha
    • 5
  • Lin-Woo Kang
    • 1
  1. 1.Department of Biological SciencesKonkuk UniversitySeoulRepublic of Korea
  2. 2.The Lawrenceville SchoolLawrencevilleUSA
  3. 3.National Leading Research Laboratory of Drug Resistance Proteomics, Department of Biological SciencesMyongji UniversityYonginRepublic of Korea
  4. 4.Department of Life ScienceSangmyung UniversitySeoulRepublic of Korea
  5. 5.Marine Biotechnology Research DivisionKorea Institute of Ocean Science and TechnologyAnsanRepublic of Korea

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