title: Molecular modeling study for interaction between Bacillus subtilis Obg and Nucleotides.
abstract: The bacterial Obg proteins (Spo0B-associated GTP-binding protein) belong to the subfamily of P-loop GTPase proteins that contain two equally and highly conserved domains, a C-terminal GTP binding domain and an N-terminal glycine-rich domain which is referred as the "Obg fold" and now it is considered as one of the new targets for antibacterial drug. When the Obg protein is associated with GTP, it becomes activated, because conformation of Obg fold changes due to the structural changes of GTPase switch elements in GTP binding site. In order to investigate the effects and structural changes in GTP bound to Obg and GTPase switch elements for activation, four different molecular dynamics (MD) simulations were performed with/without the three different nucleotides (GTP, GDP, and GDP + Pi) using the Bacillus subtilis Obg (BsObg) structure. The protein structures generated from the four different systems were compared using their representative structures. The pattern of C(alpha)-C(alpha) distance plot and angle between the two Obg fold domains of simulated apo form and each system (GTP, GDP, and GDP+Pi) were significantly different in the GTP-bound system from the others. The switch 2 element was significantly changed in GTP-bound system. Also root-mean-square fluctuation (RMSF) analysis revealed that the flexibility of the switch 2 element region was much higher than the others. This was caused by the characteristic binding mode of the nucleotides. When GTP was bound to Obg, its gamma-phosphate oxygen was found to interact with the key residue (D212) of the switch 2 element, on the contrary there was no such interaction found in other systems. Based on the results, we were able to predict the possible binding conformation of the activated form of Obg with L13, which is essential for the assembly with ribosome.
authors.affiliation: Division of Applied Life Science, Environmental Biotechnology National Core Research Center, Plant Molecular Biology and Biotechnology Research Center, Gyeongsang National University, Jinju, Gyeongsangnam-do, Republic of Korea.
authors.forename: Yuno
authors.initials: Y
authors.lastname: Lee
authors.forename: Woo Young
authors.initials: WY
authors.lastname: Bang
authors.forename: Songmi
authors.initials: S
authors.lastname: Kim
authors.forename: Prettina
authors.initials: P
authors.lastname: Lazar
authors.forename: Chul Wook
authors.initials: CW
authors.lastname: Kim
authors.forename: Jeong Dong
authors.initials: JD
authors.lastname: Bahk
authors.forename: Keun Woo
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D001426:Bacterial Proteins; D009711:Nucleotides; C090542:Obg GTP-binding protein, Bacteria; D019204:GTP-Binding Proteins