7SHJ

Crystal structure of Acinetobacter baumannii ZnuA in the metal-free state

Summary for 7SHJ

• Entry DOI: 10.2210/pdb7shj/pdb
• Descriptor: Zinc ABC transporter solute-binding protein, SODIUM ION (3 entities in total)
• Functional Keywords: zinc, solute-binding protein, abc transporter, host-pathogen, znua, metal binding protein
• Biological source: Acinetobacter baumannii
• Total number of polymer chains: 2
• Total formula weight: 64089.39

Authors

Luo, Z.,McDevitt, C.A.,Kobe, B. (deposition date: 2021-10-09, release date: 2022-10-12, Last modification date: 2024-10-30)

Primary citation

Alquethamy, S.,Ganio, K.,Luo, Z.,Hossain, S.I.,Hayes, A.J.,Ve, T.,Davies, M.R.,Deplazes, E.,Kobe, B.,McDevitt, C.A.
Structural and biochemical characterization of Acinetobacter baumannii ZnuA.
J.Inorg.Biochem., 231:111787-111787, 2022

PubMed Abstract: Acinetobacter baumannii is a Gram-negative nosocomial pathogen associated with significant disease. Crucial to the survival and pathogenesis of A. baumannii is the ability to acquire essential micronutrients such as Zn(II). Recruitment of Zn(II) by A. baumannii is mediated, at least in part, by the periplasmic solute-binding protein ZnuA and the ATP-binding cassette transporter ZnuBC. Here, we combined genomic, biochemical, and structural approaches to characterize A. baumannii AB5075_UW ZnuA. Bioinformatic analyses using a diverse collection of A. baumannii genomes determined that ZnuA is highly conserved, with the binding site comprised by three strictly conserved histidine residues. The structure of metal-free ZnuA was determined at 2.1 Å resolution, with molecular dynamics analyses revealing loop α2β2, which harbors the putative Zn(II)-coordinating residue His41, to be highly mobile in the metal-free state. The contribution of the putative binding site histidine residues to Zn(II) interaction was further probed by mutagenesis. Analysis of ZnuA mutant variants was performed by quantitative metal binding assays, differential scanning fluorimetry, and affinity measurements, which showed that all three histidine residues contributed to Zn(II)-recruitment, albeit to different extents. Collectively, these analyses provide insight into the mechanism of Zn(II)-binding by A. baumannii ZnuA and expand our understanding of the functional diversity of Zn(II)-recruiting proteins.

PubMed: 35303613
DOI: 10.1016/j.jinorgbio.2022.111787

Experimental method

X-RAY DIFFRACTION (2.13 Å)