Shumayrikh Nisreen, Huang Yu Chuan, Sen Dipankar
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
Nucleic Acids Res. 2015 Apr 30;43(8):4191-201. doi: 10.1093/nar/gkv266. Epub 2015 Mar 30.
Guanine-rich, single-stranded, DNAs and RNAs are able to fold to form G-quadruplexes that are held together by guanine base quartets. G-quadruplexes are known to bind ferric heme [Fe(III)-protoporphyrin IX] and to strongly activate such bound hemes toward peroxidase (1-electron oxidation) as well as oxygenase/peroxygenase (2-electron oxidation) activities. However, much remains unknown about how such activation is effected. Herein, we investigated whether G-quadruplexes were strictly required for heme activation or whether related multi-stranded DNA/RNA structures such as isoguanine (iG) quadruplexes and pentaplexes could also bind and activate heme. We found that iG-pentaplexes did indeed bind and activate heme comparably to G-quadruplexes; however, iG-quadruplexes did neither. Earlier structural and computational studies had suggested that while the geometry of backbone-unconstrained iG-quintets templated by cations such as Na(+) or NH4 (+) was planar, that of iG-quartets deviated from planarity. We hypothesize that the binding as well as activation of heme by DNA or RNA is strongly supported by the planarity of the nucleobase quartet or quintet that interacts directly with the heme.
富含鸟嘌呤的单链DNA和RNA能够折叠形成由鸟嘌呤碱基四重体维系在一起的G-四链体。已知G-四链体能够结合铁血红素[Fe(III)-原卟啉IX]，并强烈激活此类结合血红素的过氧化物酶（单电子氧化）以及加氧酶/过氧合酶（双电子氧化）活性。然而，关于这种激活是如何实现的，仍有许多未知之处。在此，我们研究了G-四链体对于血红素激活是否是严格必需的，或者诸如异鸟嘌呤（iG）四链体和五链体等相关的多链DNA/RNA结构是否也能结合并激活血红素。我们发现iG-五链体确实能够与G-四链体一样结合并激活血红素；然而，iG-四链体却不能。早期的结构和计算研究表明，虽然由诸如Na(+)或NH4(+)等阳离子模板化的无骨架约束的iG-五联体的几何形状是平面的，但iG-四重体的几何形状却偏离平面。我们推测，与血红素直接相互作用的核碱基四重体或五重体的平面性有力地支持了DNA或RNA对血红素的结合以及激活。
