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Article

Structural and Functional Insights into the Biofilm-Associated BceF Tyrosine Kinase Domain from Burkholderia cepacia

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Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel
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Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
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Entoprotech Ltd., 2 Ner Halayla, Caesarea 3088900, Israel
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Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel
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Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th Street, San Francisco, CA 94143-2550, USA
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Kamari Pharma, Nes Ziona 7403626, Israel
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Institute of Animal Science, Volcani Institute, Agricultural Research Organization, Rishon LeZiyon 7528809, Israel
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European Molecular Biology Laboratory (EMBL), 22607 Hamburg, Germany
*
Authors to whom correspondence should be addressed.
Academic Editor: Maria Stefania Sinicropi
Biomolecules 2021, 11(8), 1196; https://doi.org/10.3390/biom11081196
Received: 11 July 2021 / Revised: 3 August 2021 / Accepted: 9 August 2021 / Published: 12 August 2021
(This article belongs to the Topic Compounds with Medicinal Value)
BceF is a bacterial tyrosine kinase (BY-kinase) from Burkholderia cepacia, a Gram-negative bacterium accountable for respiratory infections in immunocompromised and cystic fibrosis patients. BceF is involved in the production of exopolysaccharides secreted to the biofilm matrix and promotes resistant and aggressive infections. BY-kinases share no homology with mammalian kinases, and thereby offer a means to develop novel and specific antivirulence drugs. Here, we report the crystal structure of the BceF kinase domain at 1.85 Å resolution. The isolated BceF kinase domain is assembled as a dimer in solution and crystallized as a dimer in the asymmetric unit with endogenous adenosine-diphosphate bound at the active sites. The low enzymatic efficiency measured in solution may be explained by the partial obstruction of the active sites at the crystallographic dimer interface. This study provides insights into self-assembly and the specific activity of isolated catalytic domains. Several unique variations around the active site compared to other BY-kinases may allow for structure-based design of specific inhibitors to target Burkholderia cepacia virulence. View Full-Text
Keywords: bacterial tyrosine kinases; Burkholderia cepacian; X-ray crystallography; antivirulence bacterial tyrosine kinases; Burkholderia cepacian; X-ray crystallography; antivirulence
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MDPI and ACS Style

Mayer, M.; Matiuhin, Y.; Nawatha, M.; Tabachnikov, O.; Fish, I.; Schutz, N.; Dvir, H.; Landau, M. Structural and Functional Insights into the Biofilm-Associated BceF Tyrosine Kinase Domain from Burkholderia cepacia. Biomolecules 2021, 11, 1196. https://doi.org/10.3390/biom11081196

AMA Style

Mayer M, Matiuhin Y, Nawatha M, Tabachnikov O, Fish I, Schutz N, Dvir H, Landau M. Structural and Functional Insights into the Biofilm-Associated BceF Tyrosine Kinase Domain from Burkholderia cepacia. Biomolecules. 2021; 11(8):1196. https://doi.org/10.3390/biom11081196

Chicago/Turabian Style

Mayer, Michal, Yulia Matiuhin, Mickal Nawatha, Orly Tabachnikov, Inbar Fish, Nili Schutz, Hay Dvir, and Meytal Landau. 2021. "Structural and Functional Insights into the Biofilm-Associated BceF Tyrosine Kinase Domain from Burkholderia cepacia" Biomolecules 11, no. 8: 1196. https://doi.org/10.3390/biom11081196

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