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Stereochemical Trajectories of a Two-Component Regulatory System PmrA/B in a Colistin-Resistant Acinetobacter baumannii Clinical Isolate

BACKGROUND: There is limited information on the 3D prediction and modeling of the colistin resistance-associated proteins PmrA/B TCS in Acinetobacter baumannii. We aimed to evaluate the stereochemical structure and domain characterization of PmrA/B in an A. baumannii isolate resistant to high-level...

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Autores principales: Kandehkar Ghahraman, Mohammad Reza, Hosseini-Nave, Hossein, Azizi, Omid, Shakibaie, Mohammad Reza, Mollaie, Hamid Reza, Shakibaie, Samane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Pasteur Institute of Iran 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183390/
https://www.ncbi.nlm.nih.gov/pubmed/33653023
http://dx.doi.org/10.52547/ibj.25.3.193
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author Kandehkar Ghahraman, Mohammad Reza
Hosseini-Nave, Hossein
Azizi, Omid
Shakibaie, Mohammad Reza
Mollaie, Hamid Reza
Shakibaie, Samane
author_facet Kandehkar Ghahraman, Mohammad Reza
Hosseini-Nave, Hossein
Azizi, Omid
Shakibaie, Mohammad Reza
Mollaie, Hamid Reza
Shakibaie, Samane
author_sort Kandehkar Ghahraman, Mohammad Reza
collection PubMed
description BACKGROUND: There is limited information on the 3D prediction and modeling of the colistin resistance-associated proteins PmrA/B TCS in Acinetobacter baumannii. We aimed to evaluate the stereochemical structure and domain characterization of PmrA/B in an A. baumannii isolate resistant to high-level colistin, using bioinformatics tools. METHODS: The species of the isolate and its susceptibility to colistin were confirmed by PCR-sequencing and MIC assay, respectively. For 3D prediction of the PmrA/B, we used 16 template models with the highest quality (e-value <1 × 10−50). RESULTS: Prediction of the PmrA structure revealed a monomeric non-redundant protein consisting of 28 α-helices and 22 β-sheets. The PmrA DNA-binding motif displayed three antiparallel α-helices, followed by three β-sheets, and was bond to the major groove of DNA by intermolecular van der Waals bonds through amino acids Lys, Asp, His, and Arg, respectively. Superimposition of the deduced PmrA 3D structure with the closely related PmrA protein model (GenBank no. WP_071210493.1) revealed no distortion in conformation, due to Glu→Lys substitution at position 218. Similarly, the PmrB protein structure displayed 24 α-helices and 13 β-sheets. In our case, His251 acted as a phosphate receptor in the HisKA domain. The amino acid substitutions were mainly observed at the putative N-terminus region of the protein. Furthermore, two substitutions (Lys21→Ser and Ser28→Arg) in the transmembrane domain were detected. CONCLUSION: TheDNA-binding motif of PmrA is highly conserved, though the N-terminal fragment of PmrB showed a high rate of base substitutions. This research provides valuable insights into the mechanism of colistin resistance in A. baumannii.
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spelling pubmed-81833902021-06-11 Stereochemical Trajectories of a Two-Component Regulatory System PmrA/B in a Colistin-Resistant Acinetobacter baumannii Clinical Isolate Kandehkar Ghahraman, Mohammad Reza Hosseini-Nave, Hossein Azizi, Omid Shakibaie, Mohammad Reza Mollaie, Hamid Reza Shakibaie, Samane Iran Biomed J Full Length BACKGROUND: There is limited information on the 3D prediction and modeling of the colistin resistance-associated proteins PmrA/B TCS in Acinetobacter baumannii. We aimed to evaluate the stereochemical structure and domain characterization of PmrA/B in an A. baumannii isolate resistant to high-level colistin, using bioinformatics tools. METHODS: The species of the isolate and its susceptibility to colistin were confirmed by PCR-sequencing and MIC assay, respectively. For 3D prediction of the PmrA/B, we used 16 template models with the highest quality (e-value <1 × 10−50). RESULTS: Prediction of the PmrA structure revealed a monomeric non-redundant protein consisting of 28 α-helices and 22 β-sheets. The PmrA DNA-binding motif displayed three antiparallel α-helices, followed by three β-sheets, and was bond to the major groove of DNA by intermolecular van der Waals bonds through amino acids Lys, Asp, His, and Arg, respectively. Superimposition of the deduced PmrA 3D structure with the closely related PmrA protein model (GenBank no. WP_071210493.1) revealed no distortion in conformation, due to Glu→Lys substitution at position 218. Similarly, the PmrB protein structure displayed 24 α-helices and 13 β-sheets. In our case, His251 acted as a phosphate receptor in the HisKA domain. The amino acid substitutions were mainly observed at the putative N-terminus region of the protein. Furthermore, two substitutions (Lys21→Ser and Ser28→Arg) in the transmembrane domain were detected. CONCLUSION: TheDNA-binding motif of PmrA is highly conserved, though the N-terminal fragment of PmrB showed a high rate of base substitutions. This research provides valuable insights into the mechanism of colistin resistance in A. baumannii. Pasteur Institute of Iran 2021-05 2021-03-03 /pmc/articles/PMC8183390/ /pubmed/33653023 http://dx.doi.org/10.52547/ibj.25.3.193 Text en https://creativecommons.org/licenses/by/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Length
Kandehkar Ghahraman, Mohammad Reza
Hosseini-Nave, Hossein
Azizi, Omid
Shakibaie, Mohammad Reza
Mollaie, Hamid Reza
Shakibaie, Samane
Stereochemical Trajectories of a Two-Component Regulatory System PmrA/B in a Colistin-Resistant Acinetobacter baumannii Clinical Isolate
title Stereochemical Trajectories of a Two-Component Regulatory System PmrA/B in a Colistin-Resistant Acinetobacter baumannii Clinical Isolate
title_full Stereochemical Trajectories of a Two-Component Regulatory System PmrA/B in a Colistin-Resistant Acinetobacter baumannii Clinical Isolate
title_fullStr Stereochemical Trajectories of a Two-Component Regulatory System PmrA/B in a Colistin-Resistant Acinetobacter baumannii Clinical Isolate
title_full_unstemmed Stereochemical Trajectories of a Two-Component Regulatory System PmrA/B in a Colistin-Resistant Acinetobacter baumannii Clinical Isolate
title_short Stereochemical Trajectories of a Two-Component Regulatory System PmrA/B in a Colistin-Resistant Acinetobacter baumannii Clinical Isolate
title_sort stereochemical trajectories of a two-component regulatory system pmra/b in a colistin-resistant acinetobacter baumannii clinical isolate
topic Full Length
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183390/
https://www.ncbi.nlm.nih.gov/pubmed/33653023
http://dx.doi.org/10.52547/ibj.25.3.193
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