Structural and biochemical characterization of Acinetobacter baumannii ZnuA

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dc.contributor.authorAlquethamy, S.
dc.contributor.authorGanio, K.
dc.contributor.authorLuo, Z.
dc.contributor.authorHossain, S.I.
dc.contributor.authorHayes, A.J.
dc.contributor.authorVe, T.
dc.contributor.authorDavies, M.R.
dc.contributor.authorDeplazes, E.
dc.contributor.authorKobe, B.
dc.contributor.authorMcDevitt, C.A.
dc.date.issued2022
dc.description.abstractAcinetobacter 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.
dc.description.statementofresponsibilitySaleh Alquethamy, Katherine Ganio, Zhenyao Luo, Sheikh I. Hossain, Andrew J. Hayes, Thomas Ve Mark R. Davies, Evelyne Deplazes, Boštjan Kobe, Christopher A. McDevitt
dc.identifier.citationJournal of Inorganic Biochemistry, 2022; 231:111787-111787
dc.identifier.doi10.1016/j.jinorgbio.2022.111787
dc.identifier.issn0162-0134
dc.identifier.issn1873-3344
dc.identifier.orcidMcDevitt, C.A. [0000-0003-1596-4841]
dc.identifier.urihttps://hdl.handle.net/2440/135563
dc.language.isoen
dc.publisherElsevier BV
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1071659
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1122582
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1180826
dc.relation.granthttp://purl.org/au-research/grants/arc/FL180100109
dc.relation.granthttp://purl.org/au-research/grants/arc/FT170100006
dc.rights© 2022 Elsevier Inc. All rights reserved.
dc.source.urihttps://doi.org/10.1016/j.jinorgbio.2022.111787
dc.subjectAcinetobacter baumannii; Zinc; Solute-binding protein; ABC transporter; ZnuA; Zinc homeostasis
dc.subject.meshAcinetobacter baumannii
dc.subject.meshZinc
dc.subject.meshHistidine
dc.subject.meshBacterial Proteins
dc.subject.meshATP-Binding Cassette Transporters
dc.subject.meshModels, Molecular
dc.titleStructural and biochemical characterization of Acinetobacter baumannii ZnuA
dc.typeJournal article
pubs.publication-statusPublished

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