title: Polyphosphate, cyclic AMP, guanosine tetraphosphate, and c-di-GMP reduce in vitro Lon activity.
abstract: Lon protease is conserved from bacteria to humans and regulates cellular processes by degrading different classes of proteins including antitoxins, transcriptional activators, unfolded proteins, and free ribosomal proteins. Since we found that Lon has several putative cyclic diguanylate (c-di-GMP) binding sites and since Lon binds polyphosphate (polyP) and lipid polysaccharide, we hypothesized that Lon has an affinity for phosphate-based molecules that might regulate its activity. Hence we tested the effect of polyP, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), guanosine tetraphosphate (ppGpp), c-di-GMP, and GMP on the ability of Lon to degrade α-casein. Inhibition of in vitro Lon activity occurred for polyP, cAMP, ppGpp, and c-di-GMP. We also demonstrated by HPLC that Lon is able to bind c-di-GMP. Therefore, four cell signals were found to regulate the activity of Lon protease.
authors.affiliation: Department of Chemical Engineering; Pennsylvania State University; University Park, PA USA.
authors.forename: Devon O
authors.initials: DO
authors.lastname: Osbourne
authors.affiliation: Department of Chemical Engineering; Pennsylvania State University; University Park, PA USA.
authors.forename: Valerie W C
authors.initials: VW
authors.lastname: Soo
authors.affiliation: Department of Molecular and Cellular Biology; Intercollegiate Faculty of Biotechnology; University of Gdansk; Gdansk, Poland.
authors.forename: Igor
authors.initials: I
authors.lastname: Konieczny
authors.affiliation: Department of Chemical Engineering; Pennsylvania State University; University Park, PA USA; Department of Biochemistry and Molecular Biology; Pennsylvania State University; University Park, PA USA.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Wood
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002364:Caseins / Q000737:chemistry; D000242:Cyclic AMP / Q000737:chemistry*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000737:chemistry; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000737:chemistry; D006159:Guanosine Tetraphosphate / Q000737:chemistry*; D008969:Molecular Sequence Data; D011122:Polyphosphates / Q000737:chemistry*; D049070:Protease La / Q000737:chemistry*; D059748:Proteolysis
chemical_list: D002364:Caseins; D029968:Escherichia coli Proteins; D011122:Polyphosphates; D006159:Guanosine Tetraphosphate; C062025:bis(3',5')-cyclic diguanylic acid; D000242:Cyclic AMP; D049070:Protease La; D006152:Cyclic GMP
keywords: Lon protease; c-di-GMP; cAMP; polyphosphate; ppGpp