Biochemical and structural characterization of two cif-like epoxide hydrolases from Burkholderia cenocepacia
Epoxide hydrolases catalyze the conversion of epoxides to vicinal diols in a range of cellular processes such as signaling, detoxification, and virulence. These enzymes typically utilize a pair of tyrosine residues to orient the substrate epoxide ring in the active site and stabilize the hydrolysis...
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2021-01-01
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doaj-5cdd23654dbb4be9938261084cd04d942021-03-07T04:30:24ZengElsevierCurrent Research in Structural Biology2665-928X2021-01-0137284Biochemical and structural characterization of two cif-like epoxide hydrolases from Burkholderia cenocepaciaNoor M. Taher0Kelli L. Hvorecny1Cassandra M. Burke2Morgan S.A. Gilman3Gary E. Heussler4Jared Adolf-Bryfogle5Christopher D. Bahl6George A. O'Toole7Dean R. Madden8Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, USADepartment of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, USADepartment of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, USADepartment of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, USADepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USAInstitute for Protein Innovation, Boston, MA, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USAInstitute for Protein Innovation, Boston, MA, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USADepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USADepartment of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA; Corresponding author. 7200 Vail Building, Room 408, Hanover, NH, 03755-3844, USA.Epoxide hydrolases catalyze the conversion of epoxides to vicinal diols in a range of cellular processes such as signaling, detoxification, and virulence. These enzymes typically utilize a pair of tyrosine residues to orient the substrate epoxide ring in the active site and stabilize the hydrolysis intermediate. A new subclass of epoxide hydrolases that utilize a histidine in place of one of the tyrosines was established with the discovery of the CFTR Inhibitory Factor (Cif) from Pseudomonas aeruginosa. Although the presence of such Cif-like epoxide hydrolases was predicted in other opportunistic pathogens based on sequence analyses, only Cif and its homolog aCif from Acinetobacter nosocomialis have been characterized. Here we report the biochemical and structural characteristics of Cfl1 and Cfl2, two Cif-like epoxide hydrolases from Burkholderia cenocepacia. Cfl1 is able to hydrolyze xenobiotic as well as biological epoxides that might be encountered in the environment or during infection. In contrast, Cfl2 shows very low activity against a diverse set of epoxides. The crystal structures of the two proteins reveal quaternary structures that build on the well-known dimeric assembly of the α/β hydrolase domain, but broaden our understanding of the structural diversity encoded in novel oligomer interfaces. Analysis of the interfaces reveals both similarities and key differences in sequence conservation between the two assemblies, and between the canonical dimer and the novel oligomer interfaces of each assembly. Finally, we discuss the effects of these higher-order assemblies on the intra-monomer flexibility of Cfl1 and Cfl2 and their possible roles in regulating enzymatic activity.http://www.sciencedirect.com/science/article/pii/S2665928X21000039α/β hydrolaseX-ray crystallographyBurkholderia cenocepaciaEpoxy-polyunsaturated fatty acidsEpoxide hydrolase |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Noor M. Taher Kelli L. Hvorecny Cassandra M. Burke Morgan S.A. Gilman Gary E. Heussler Jared Adolf-Bryfogle Christopher D. Bahl George A. O'Toole Dean R. Madden |
spellingShingle |
Noor M. Taher Kelli L. Hvorecny Cassandra M. Burke Morgan S.A. Gilman Gary E. Heussler Jared Adolf-Bryfogle Christopher D. Bahl George A. O'Toole Dean R. Madden Biochemical and structural characterization of two cif-like epoxide hydrolases from Burkholderia cenocepacia Current Research in Structural Biology α/β hydrolase X-ray crystallography Burkholderia cenocepacia Epoxy-polyunsaturated fatty acids Epoxide hydrolase |
author_facet |
Noor M. Taher Kelli L. Hvorecny Cassandra M. Burke Morgan S.A. Gilman Gary E. Heussler Jared Adolf-Bryfogle Christopher D. Bahl George A. O'Toole Dean R. Madden |
author_sort |
Noor M. Taher |
title |
Biochemical and structural characterization of two cif-like epoxide hydrolases from Burkholderia cenocepacia |
title_short |
Biochemical and structural characterization of two cif-like epoxide hydrolases from Burkholderia cenocepacia |
title_full |
Biochemical and structural characterization of two cif-like epoxide hydrolases from Burkholderia cenocepacia |
title_fullStr |
Biochemical and structural characterization of two cif-like epoxide hydrolases from Burkholderia cenocepacia |
title_full_unstemmed |
Biochemical and structural characterization of two cif-like epoxide hydrolases from Burkholderia cenocepacia |
title_sort |
biochemical and structural characterization of two cif-like epoxide hydrolases from burkholderia cenocepacia |
publisher |
Elsevier |
series |
Current Research in Structural Biology |
issn |
2665-928X |
publishDate |
2021-01-01 |
description |
Epoxide hydrolases catalyze the conversion of epoxides to vicinal diols in a range of cellular processes such as signaling, detoxification, and virulence. These enzymes typically utilize a pair of tyrosine residues to orient the substrate epoxide ring in the active site and stabilize the hydrolysis intermediate. A new subclass of epoxide hydrolases that utilize a histidine in place of one of the tyrosines was established with the discovery of the CFTR Inhibitory Factor (Cif) from Pseudomonas aeruginosa. Although the presence of such Cif-like epoxide hydrolases was predicted in other opportunistic pathogens based on sequence analyses, only Cif and its homolog aCif from Acinetobacter nosocomialis have been characterized. Here we report the biochemical and structural characteristics of Cfl1 and Cfl2, two Cif-like epoxide hydrolases from Burkholderia cenocepacia. Cfl1 is able to hydrolyze xenobiotic as well as biological epoxides that might be encountered in the environment or during infection. In contrast, Cfl2 shows very low activity against a diverse set of epoxides. The crystal structures of the two proteins reveal quaternary structures that build on the well-known dimeric assembly of the α/β hydrolase domain, but broaden our understanding of the structural diversity encoded in novel oligomer interfaces. Analysis of the interfaces reveals both similarities and key differences in sequence conservation between the two assemblies, and between the canonical dimer and the novel oligomer interfaces of each assembly. Finally, we discuss the effects of these higher-order assemblies on the intra-monomer flexibility of Cfl1 and Cfl2 and their possible roles in regulating enzymatic activity. |
topic |
α/β hydrolase X-ray crystallography Burkholderia cenocepacia Epoxy-polyunsaturated fatty acids Epoxide hydrolase |
url |
http://www.sciencedirect.com/science/article/pii/S2665928X21000039 |
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