Guanine-rich RNAs and DNAs that bind heme robustly catalyze oxygen transfer reactions.
Diverse guanine-rich RNAs and DNAs that fold to form guanine quadruplexes are known to form tight complexes with Fe(III) heme. We show here that a wide variety of such complexes robustly catalyze two-electron oxidations, transferring oxygen from hydrogen peroxide to thioanisole, indole, and styrene substrates. Use of (18)O-labeled hydrogen peroxide reveals the source of the oxygen transferred to form thioanisole sulfoxide and styrene oxide to be the activated ferryl moiety within these systems. Hammett analysis of the kinetics of thioanisole sulfoxide formation is unable to distinguish between a one-step, direct oxygen transfer and a two-step, oxygen rebound mechanism for this catalysis. Oxygen transfer to indole produces a range of products, including indigo and related dyes. Docking of heme onto a high-resolution structure of the G-quadruplex fold of Bcl-2 promoter DNA, which both binds heme and transfers oxygen, suggests a relatively open active site for this class of ribozymes and deoxyribozymes. That heme-dependent catalysis of oxygen transfer is a property of many RNAs and DNAs has ramifications for primordial evolution, enzyme design, cellular oxidative disease, and anticancer therapeutics.
Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
Lester C-H
LC
Poon
Stephen P
SP
Methot
William
W
Morabi-Pazooki
Frédéric
F
Pio
Andrew J
AJ
Bennet
Dipankar
D
Sen
D000079:Acetaldehyde / Q000031:analogs & derivatives / Q000737:chemistry; D002384:Catalysis; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006418:Heme / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry; D007211:Indoles / Q000737:chemistry; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D020058:Styrene / Q000737:chemistry; D013440:Sulfides / Q000737:chemistry
D007211:Indoles; D013440:Sulfides; D006418:Heme; D020058:Styrene; D012313:RNA; C030374:indole; D004247:DNA; C093850:methylphenylsulfide; D006861:Hydrogen Peroxide; D000079:Acetaldehyde; D010100:Oxygen; C013192:phenylacetaldehyde