title: Energetics and kinetics of a conformational switch in G-quadruplex DNA.
abstract: Circular dichroism and differential scanning calorimetry were used to determine the energetics of the conformational switch of the human telomere quadruplex formed by the sequence d[AGGG(TTAGGG)3] between the sodium basket form and the potassium hybrid form. The energy barrier separating the two conformations was found to be modest, only 1.4-2.4 kcal mol(-1). The kinetics of exchange of bound K+ for Na+ cations and the concomitant conformational switch was assessed by measuring time-dependent changes in the circular dichroism spectrum accompanying the cation exchange reaction. The time course of these changes was found to consist of three distinct kinetic processes: a rapid phase that was complete in less than 5 ms followed by two slower phases with relaxation times of 40-50 s and 600-800 s at 25 degrees C and pH 7.0. We interpret these kinetics in terms of a model in which the bound Na+ cations are rapidly replaced by K+ followed by relatively slow structural rearrangements to generate the final K(+)-bound product(s). Circular dichroism studies showed that addition of the porphyrin TmPyP4 promoted conversion of the basket to the hybrid form. The kinetics of the TmPyP4-induced conformational change were the same as those observed for the cation exchange reaction.
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, 529 South Jackson Street, Louisville, Kentucky 40202, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Gray
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Chaires
mesh_terms: D001703:Biophysics / Q000379:methods*; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002412:Cations; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D007700:Kinetics; D015233:Models, Statistical; D008968:Molecular Conformation; D011188:Potassium / Q000737:chemistry; D012964:Sodium / Q000737:chemistry; D016615:Telomere / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics
chemical_list: D002412:Cations; D004247:DNA; D012964:Sodium; D011188:Potassium
references.citation: Adv Protein Chem. 1975;29:1-83
references.pmid: 1136898
references.citation: Photochem Photobiol Sci. 2008 Aug;7(8):948-55
references.pmid: 18688502
references.citation: Biochemistry. 1999 Dec 7;38(49):16067-75
references.pmid: 10587429
references.citation: Nature. 1990 Mar 29;344(6265):410-4
references.pmid: 2320109
references.citation: J Am Chem Soc. 2005 Jul 6;127(26):9439-47
references.pmid: 15984871
references.citation: Eur Biophys J. 1997;26(6):419-26
references.pmid: 9404005
references.citation: Nucleic Acids Symp Ser (Oxf). 2008;(52):409-10
references.pmid: 18776427
references.citation: J Biochem Biophys Methods. 1994 Jan;28(1):1-33
references.pmid: 8151067
references.citation: Biochemistry. 1985 Dec 3;24(25):7479-86
references.pmid: 4084594
references.citation: Biochemistry. 1999 Jun 1;38(22):6981-6
references.pmid: 10353809
references.citation: Nucleic Acids Res. 2008 Jul;36(12):4191-203
references.pmid: 18567908
references.citation: Biochimie. 2008 Aug;90(8):1172-83
references.pmid: 18373984
references.citation: Methods Enzymol. 2001;340:99-108
references.pmid: 11494877
references.citation: J Mol Biol. 1996 Jan 26;255(3):476-83
references.pmid: 8568891
references.citation: Nucleic Acids Res. 2007;35(19):6517-25
references.pmid: 17895279
references.citation: Nucleic Acids Res. 2007;35(15):4927-40
references.pmid: 17626043
references.citation: Bioorg Med Chem. 2006 Aug 15;14(16):5584-91
references.pmid: 16682210
references.citation: Nucleic Acids Res. 2006 May 19;34(9):2723-35
references.pmid: 16714449
references.citation: ACS Chem Biol. 2008 Apr 18;3(4):207-9
references.pmid: 18422302
references.citation: Structure. 1993 Dec 15;1(4):263-82
references.pmid: 8081740
references.citation: Nucleic Acids Res. 2008 Oct;36(17):5695-703
references.pmid: 18776218
references.citation: Biochemistry. 1980 Dec 23;19(26):5998-6005
references.pmid: 6258628
references.citation: Nucleic Acids Res. 2008 Oct;36(17):5482-515
references.pmid: 18718931
references.citation: Biochemistry. 1985 Dec 3;24(25):7471-9
references.pmid: 2417627
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12032-7
references.pmid: 11027298
references.citation: Nucleic Acids Res. 2005 Aug 16;33(14):4649-59
references.pmid: 16106044
references.citation: Methods Enzymol. 2004;384:1-8
references.pmid: 15081677
references.citation: Anticancer Drug Des. 1999 Aug;14(4):317-26
references.pmid: 10625924
references.citation: Nucleic Acids Res. 2006;34(19):5402-15
references.pmid: 17012276
references.citation: Biochemistry. 1985 Dec 3;24(25):7462-71
references.pmid: 4084593
references.citation: J Am Chem Soc. 2003 Jan 22;125(3):662-6
references.pmid: 12526665
references.citation: Nature. 1979 Apr 5;278(5704):521-4
references.pmid: 372825
references.citation: Biopolymers. 1997;44(3):283-308
references.pmid: 9591480
references.citation: J Am Chem Soc. 2008 Mar 19;130(11):3590-602
references.pmid: 18293981
references.citation: J Biol Chem. 1986 Jul 5;261(19):8899-907
references.pmid: 3722181
references.citation: Nature. 2002 Jun 20;417(6891):876-80
references.pmid: 12050675
references.citation: Nucleic Acids Res. 2007;35(22):7429-55
references.pmid: 17913750
references.citation: Proc Natl Acad Sci U S A. 1962 Dec 15;48:2013-8
references.pmid: 13947099
references.citation: Biopolymers. 2008 Apr;89(4):302-9
references.pmid: 18183583
references.citation: Proc Natl Acad Sci U S A. 1972 Dec;69(12):3805-9
references.pmid: 4509343
references.citation: Angew Chem Int Ed Engl. 2007;46(28):5405-7
references.pmid: 17562537