title: Molecular dynamics simulation of the Staphylococcus aureus YsxC protein: molecular insights into ribosome assembly and allosteric inhibition of the protein.
abstract: YsxC from Staphylococcus aureus is a member of the GTPase protein family, and is involved in the ribosomal assembly and stability of this microorganism through its interactions with the L17, S2 and S10 ribosomal proteins. Inhibition of its interactions with L17, S2, S10 and the β' subunit of RNA polymerase influences ribosomal assembly, which may affect the growth of the microorganism. This makes YsxC a novel target for the design of inhibitors to treat the disease caused by S. aureus. Understanding the interaction mechanism between YsxC and its partners would aid in the identification of potential catalytic residues, which could then be targeted to inhibit its function. Accordingly, in the present study, an in silico analysis of the interactions between YsxC and L17, S2 and S10 was performed, and the potential residues involved in these interactions were identified. Based on the simulation results, a possible mechanism for the interactions between these proteins was also proposed. Finally, six ligands from among a library of 81,000 chemical molecules were found to interact with parts of the G2 and switch II regions of the YsxC protein. Moreover, their interactions with the YsxC protein were observed to provoke changes at its GTP-binding site, which suggests that the binding of these ligands leads to a reduction in GTPase activity, and they were also found to affect the interactions of YsxC with its partners. This observation indicates that the proposed interacting site of YsxC may act as an allosteric site, and disrupting interactions at this site might lead to novel allosteric inhibition of the YsxC protein.
authors.affiliation: Centre of Excellence in Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry 605 014, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Goyal
authors.forename: Kannan
authors.initials: K
authors.lastname: Muthu
authors.forename: Manivel
authors.initials: M
authors.lastname: Panneerselvam
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Pole
authors.forename: Krishna
authors.initials: K
authors.lastname: Ramadas
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000495:Allosteric Site / Q000187:drug effects; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D008024:Ligands; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D012269:Ribosomal Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000201:enzymology*; D054852:Small Molecule Libraries / Q000494:pharmacology* / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000737:chemistry / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; D012269:Ribosomal Proteins; D054852:Small Molecule Libraries; C032493:ribosomal protein L17; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases