title: Mutation of Arg191 in FtsZ Impairs Cytokinetic Abscission of Bacillus subtilis Cells.
abstract: FtsZ monomers assemble to form a dynamic Z-ring at the midcell position in bacteria that coordinates bacterial cell division. Antibacterial agents plumbagin and SB-RA-2001 were found to bind to FtsZ and to inhibit Z-ring formation in bacteria. Docking analysis indicated similar binding regions for these two inhibitors on FtsZ, and residue R191 was involved in the binding interaction with both compounds. In this work, the importance of R191 in FtsZ assembly and in bacterial cell division was analyzed. R191A-FtsZ exhibited significantly poorer polymerization ability. Further, the mutant FtsZ could poison the assembly of wild-type FtsZ (WT-FtsZ). The expression of R191A-FtsZ in Bacillus subtilis strain PL2084 perturbed Z-ring formation and produced filamentous cells, indicating that the mutation hindered the division of these cells. The results suggested that the R191A mutation is a dominant negative mutation of FtsZ. Molecular dynamics simulations of R191A-FtsZ and WT-FtsZ revealed a kink in helices H5 and H7 in the active site of R191A-FtsZ compared to that of WT-FtsZ, which is required for FtsZ assembly. The findings suggested that R191 is an important residue for FtsZ assembly, which can be targeted for the design of FtsZ inhibitors.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai 400076, India.
authors.forename: Hemendra Pal Singh
authors.initials: HP
authors.lastname: Dhaked
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai 400076, India.
authors.forename: Anusri
authors.initials: A
authors.lastname: Bhattacharya
authors.affiliation: IITB-Monash Research Academy, Indian Institute of Technology Bombay , Mumbai 400076, India.
authors.forename: Saroj
authors.initials: S
authors.lastname: Yadav
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai 400076, India.
authors.forename: Sarath Chandra
authors.initials: SC
authors.lastname: Dantu
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai 400076, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai 400076, India.
authors.forename: Dulal
authors.initials: D
authors.lastname: Panda
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001120:Arginine / Q000737:chemistry*; D001412:Bacillus subtilis / Q000166:cytology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry*; D002942:Circular Dichroism; D048749:Cytokinesis; D003598:Cytoskeletal Proteins / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D056004:Molecular Dynamics Simulation; D058105:Polymerization; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria; D001120:Arginine