PMID- 34439861
OWN - NLM
STAT- MEDLINE
DCOM- 20210922
LR  - 20210922
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 11
IP  - 8
DP  - 2021 Aug 12
TI  - Structural and Functional Insights into the Biofilm-Associated BceF Tyrosine 
      Kinase Domain from Burkholderia cepacia.
LID - 10.3390/biom11081196 [doi]
LID - 1196
AB  - 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 A 
      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.
FAU - Mayer, Michal
AU  - Mayer M
AUID- ORCID: 0000-0003-2500-6743
AD  - Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, 
      Israel.
AD  - Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 
      7610001, Israel.
FAU - Matiuhin, Yulia
AU  - Matiuhin Y
AUID- ORCID: 0000-0003-4604-4140
AD  - Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, 
      Israel.
AD  - Entoprotech Ltd., 2 Ner Halayla, Caesarea 3088900, Israel.
FAU - Nawatha, Mickal
AU  - Nawatha M
AD  - Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, 
      Israel.
FAU - Tabachnikov, Orly
AU  - Tabachnikov O
AD  - Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, 
      Israel.
FAU - Fish, Inbar
AU  - Fish I
AD  - Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life 
      Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.
AD  - Department of Pharmaceutical Chemistry, University of California San Francisco, 
      1700 4th Street, San Francisco, CA 94143-2550, USA.
FAU - Schutz, Nili
AU  - Schutz N
AD  - Kamari Pharma, Nes Ziona 7403626, Israel.
FAU - Dvir, Hay
AU  - Dvir H
AUID- ORCID: 0000-0002-5024-5626
AD  - Institute of Animal Science, Volcani Institute, Agricultural Research 
      Organization, Rishon LeZiyon 7528809, Israel.
FAU - Landau, Meytal
AU  - Landau M
AUID- ORCID: 0000-0002-1743-3430
AD  - Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, 
      Israel.
AD  - European Molecular Biology Laboratory (EMBL), 22607 Hamburg, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210812
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (Bacterial Proteins)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Bacterial Proteins/*chemistry/*physiology
MH  - Biofilms/*growth & development
MH  - Burkholderia cepacia/*physiology
MH  - Crystallography, X-Ray/methods
MH  - Humans
MH  - Protein Structure, Secondary
MH  - Protein Structure, Tertiary
MH  - Protein-Tyrosine Kinases/*chemistry/*physiology
MH  - Virulence/physiology
PMC - PMC8394532
OTO - NOTNLM
OT  - Burkholderia cepacian
OT  - X-ray crystallography
OT  - antivirulence
OT  - bacterial tyrosine kinases
COIS- The authors declare no conflict of interest.
EDAT- 2021/08/28 06:00
MHDA- 2021/09/23 06:00
PMCR- 2021/08/12
CRDT- 2021/08/27 01:05
PHST- 2021/07/11 00:00 [received]
PHST- 2021/08/03 00:00 [revised]
PHST- 2021/08/09 00:00 [accepted]
PHST- 2021/08/27 01:05 [entrez]
PHST- 2021/08/28 06:00 [pubmed]
PHST- 2021/09/23 06:00 [medline]
PHST- 2021/08/12 00:00 [pmc-release]
AID - biom11081196 [pii]
AID - biomolecules-11-01196 [pii]
AID - 10.3390/biom11081196 [doi]
PST - epublish
SO  - Biomolecules. 2021 Aug 12;11(8):1196. doi: 10.3390/biom11081196.