title: Higher-order human telomeric G-quadruplex DNA metalloenzymes enhance enantioselectivity in the Diels-Alder reaction.
abstract: Short human telomeric (HT) DNA sequences form single G-quadruplex (G4 ) units and exhibit structure-based stereocontrol for a series of reactions. However, for more biologically relevant higher-order HT G4 -DNAs (beyond a single G4 unit), the catalytic performances are unknown. Here, we found that higher-order HT G4 -DNA copper metalloenzymes (two or three G4 units) afford remarkably higher enantioselectivity (>90 % ee) and a five- to sixfold rate increase, compared to a single G4 unit, for the Diels-Alder reaction. Electron paramagnetic resonance (EPR) and enzymatic kinetic studies revealed that the distinct catalytic function between single and higher-order G4 -DNA copper metalloenzymes can be attributed to different Cu(II) coordination environments and substrate specificity. Our finding suggests that, like protein enzymes and ribozymes, higher-order structural organization is crucial for G4 -DNA-based catalysis.
authors: State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023 (China); University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049 (China).
authors: Yinghao
authors: Y
authors: Li
authors: Guoqing
authors: G
authors: Jia
authors: Changhao
authors: C
authors: Wang
authors: Mingpan
authors: M
authors: Cheng
authors: Can
authors: C
authors: Li
mesh_terms: D001483:Base Sequence; D002384:Catalysis; D003300:Copper / Q000378:metabolism; D061565:Cycloaddition Reaction; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D054856:G-Quadruplexes; D006801:Humans; D007700:Kinetics; D008667:Metalloproteins / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D008667:Metalloproteins; D003300:Copper; D004247:DNA
keywords: DNA; Diels-Alder reaction; G-quadruplexes; enantioselective catalysis; human telomeric DNA; metalloenzyme