Universität zu Köln

Wen, Yurong ORCID: 0000-0001-8730-5197, Ouyang, Zhenlin, Yu, Yue, Zhou, Xiaorong, Pei, Yingmei, Devreese, Bart ORCID: 0000-0002-9764-2581, Higgins, Paul G. ORCID: 0000-0001-8677-9454 and Zheng, Fang (2017). Mechanistic insight into how multidrug resistant Acinetobacter baumannii response regulator AdeR recognizes an intercistronic region. Nucleic Acids Res., 45 (16). S. 9773 - 9788. OXFORD: OXFORD UNIV PRESS. ISSN 1362-4962

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Abstract

AdeR-AdeS is a two-component regulatory system, which controls expression of the adeABC efflux pump involved in Acinetobacter baumannii multidrug resistance. AdeR is a response regulator consisting of an N-terminal receiver domain and a C-terminal DNA-binding-domain. AdeR binds to a direct-repeat DNA in the intercistronic region between adeR and adeABC. We demonstrate a markedly high affinity binding between unphosphorylated AdeR and DNA with a dissociation constant of 20 nM. In addition, we provide a 2.75 angstrom crystal structure of AdeR DNA-binding-domain complexed with the intercistronic DNA. This structure shows that the alpha 3 and beta hairpin formed by beta 5-beta 6 interacts with the major and minor groove of the DNA, which in turn leads to the introduction of a bend. The AdeR receiver domain structure revealed a dimerization motif mediated by a gearwheel-like structure involving the D108F109-R122 motif through cation pi stack interaction. The structure of AdeR receiver domain bound with magnesium indicated a conserved Glu19Asp20-Asp63 magnesium-binding motif, and revealed that the potential phosphorylation site Asp63(OD1) forms a hydrogen bond with Lys112. We thus dissected the mechanism of how AdeR recognizes the intercistronic DNA, which leads to a diverse mode of response regulation. Unlocking the AdeRS mechanism provides ways to circumvent A. baumannii antibiotic resistance.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wen, Yurong UNSPECIFIED orcid.org/0000-0001-8730-5197 UNSPECIFIED Ouyang, Zhenlin UNSPECIFIED UNSPECIFIED UNSPECIFIED Yu, Yue UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhou, Xiaorong UNSPECIFIED UNSPECIFIED UNSPECIFIED Pei, Yingmei UNSPECIFIED UNSPECIFIED UNSPECIFIED Devreese, Bart UNSPECIFIED orcid.org/0000-0002-9764-2581 UNSPECIFIED Higgins, Paul G. UNSPECIFIED orcid.org/0000-0001-8677-9454 UNSPECIFIED Zheng, Fang UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-217607
DOI:	10.1093/nar/gkx624
Journal or Publication Title:	Nucleic Acids Res.
Volume:	45
Number:	16
Page Range:	S. 9773 - 9788
Date:	2017
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1362-4962
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MOLECULAR-REPLACEMENT; DNA-BINDING; DOMAIN; TIGECYCLINE; ADEABC; OVEREXPRESSION; ACTIVATION; EXPRESSION; SCATTERING; PROTEINS Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21760