title: Mathematical model of the binding of allosteric effectors to the Escherichia coli PII signal transduction protein GlnB.
abstract: PII proteins are important regulators of nitrogen metabolism in a wide variety of organisms: the binding of the allosteric effectors ATP, ADP, and 2-oxoglutarate (2-OG) to PII proteins affects their ability to interact with target proteins. We modeled the simultaneous binding of ATP, ADP, and 2-OG to one PII protein, namely GlnB of Escherichia coli, using a modeling approach that allows the prediction of the proportions of individual binding states. Four models with different binding rules were compared. We selected one of these models (that assumes that the binding of the first nucleotide to GlnB makes it harder for subsequent nucleotides to bind) and used it to explore how physiological concentrations of ATP, ADP, and 2-OG would affect the proportions of those states of GlnB that interact with the target proteins ATase and NtrB. Our simulations indicate that GlnB can, as suggested by previous researchers, act as a sensor of both 2-OG and the ATP:ADP ratio. We conclude that our modeling approach will be an important tool in future studies concerning the PII binding states and their interactions with target proteins.
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Cx.P. 19046 Centro Politécnico, Curitiba 81531-980, Paraná, Brazil.
authors.forename: Ricardo Alves
authors.initials: RA
authors.lastname: da Rocha
authors.forename: Thiago André
authors.initials: TA
authors.lastname: Weschenfelder
authors.forename: Fernanda
authors.initials: F
authors.lastname: de Castilhos
authors.forename: Emanuel Maltempi
authors.initials: EM
authors.lastname: de Souza
authors.forename: Luciano Fernandes
authors.initials: LF
authors.lastname: Huergo
authors.forename: David Alexander
authors.initials: DA
authors.lastname: Mitchell
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008962:Models, Theoretical; D009097:Multienzyme Complexes / Q000378:metabolism; D051922:PII Nitrogen Regulatory Proteins / Q000737:chemistry* / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C582443:GlnB protein, E coli; D007656:Ketoglutaric Acids; D008024:Ligands; D009097:Multienzyme Complexes; D051922:PII Nitrogen Regulatory Proteins; C578385:glnL protein, E coli; C404143:PIID regulatory protein, Bacteria; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases