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 SCIE SCOPUS KCI

Cited 2 time in WEB OF SCIENCE Cited 2 time in Scopus
Title
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
Author(s)
Huynh, Kim-Hung; Hong, Myoung-ki; Lee, Clarice; Tran, Huyen-Thi; Lee, Sang Hee; Ahn, Yeh-Jin; Cha, Sun-Shin; Kang, Lin-Woo
Publication Year
2015-11
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 . 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.
ISSN
1225-8873
URI
https://sciwatch.kiost.ac.kr/handle/2020.kiost/2376
DOI
10.1007/s12275-015-5475-8
Bibliographic Citation
JOURNAL OF MICROBIOLOGY, v.53, no.11, pp.776 - 782, 2015
Publisher
MICROBIOLOGICAL SOCIETY KOREA
Subject
ALANYL-D-ALANINE; ANTIBIOTIC D-CYCLOSERINE; ENZYMATIC SYNTHESIS; INHIBITION; SYNTHETASE; MECHANISM; PATHOGEN; DDLB
Keywords
D-alanine-D-alanine ligase; drug target; bacterial cell wall synthesis; Acinetobacter baumannii; X-ray crystallography
Type
Article
Language
English
Document Type
Article
Publisher
MICROBIOLOGICAL SOCIETY KOREA
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