High‐Resolution Crystal Structure of a Silver(I)–RNA Hybrid Duplex Containing Watson–Crick‐like CSilver(I)C Metallo‐Base Pairs

Abstract

Metallo-base pairs have been extensively studied for applications in nucleic acid-based nanodevices and genetic code expansion. Metallo-base pairs composed of natural nucleobases are attractive because nanodevices containing natural metallo-base pairs can be easily prepared from commercially available sources. Previously, we have reported a crystal structure of a DNA duplex containing T-Hg(II)-T base pairs. Herein, we have determined a high-resolution crystal structure of the second natural metallo-base pair between pyrimidine bases C-Ag(I)-C formed in an RNA duplex. One Ag(I) occupies the center between two cytosines and forms a C-Ag(I)-C base pair through N3-Ag(I)-N3 linear coordination. The C-Ag(I)-C base pair formation does not disturb the standard A-form conformation of RNA. Since the C-Ag(I)-C base pair is structurally similar to the canonical Watson-Crick base pairs, it can be a useful building block for structure-based design and fabrication of nucleic acid-based nanodevices.

Flexibility and stabilization of HgII-mediated C:T and T:T base pairs in DNA duplex

“…The DNA1–Hg II represents the first DNA structure carrying the C–Hg II –T pairs to date; it reveals that the exocyclic N4 atom can also interact with the Hg II ion. Though we failed to capture it in our study, the structure of the RNA duplex carrying the C–Ag I –C pair suggested that the N3 atom of the C residue has the potential to coordinate with the Hg II ion (32). Together, these observations advanced our understanding on the Hg II -mediated metallo-base pairs.…”

“…In the reported 12TT DNA structure (33) and the C–Ag I –C pair containing RNA structure (32), the metallo-base pairs are mainly stabilized by the N3–Hg II –N3 and N3–Ag I –N3 interactions, respectively. Interestingly, besides the Hg II -mediated interactions, we observed that the conformation of the C3–T6* pair is also stabilized by one water molecule located at the minor grove of the DNA1–Hg II structure (Figure 2B).…”

“…The C:C mispair has been structural characterized previously (32); with the help of two water molecules, the C:C mispair adopts a Watson–Crick like geometry. Though it did not form in the apo- 12TT DNA structure, the T–T mispair was captured in our apo- DNA3 structure at high resolution (Figure 6); in the structure, the T–T mispair adopts a wobble like geometry, and the presence of this mispair does not cause significant conformational perturbation comparing to the native DNA duplex.…”

“…Particularly for the X-ray crystal structures, there is only one HIV-1 RNA dimerization initiation site that captured a G–Au III –C pair (27), one RNA duplex containing C–Ag I –C pair (32), and one DNA duplex (12TT) containing two consecutive T–Hg II –T pairs (33) reported previously; interestingly, in the latter two structures, formation of the metallo-base pairs involves the homo-pyrimidine mispairs, C:C and T:T pairs. Similar to the homo-pyrimidine mispairs, C:T pair, the hetero-pyrimidne mispair, can also occur in vivo as a consequence of either replication errors or heteroduplex formation in the course of genetic recombination (34).…”

pH-Dependence of the thermal stability of metallo-DNA duplexes containing ligand-type 5-hydroxyuracil nucleobases

“…thymine (T) and cytosine (C)) are known to form an Hg(II)-or Ag(I)-mediated base pair, in which N3 atoms coordinate to the metal ion (i.e. T-Hg(II)-T [8][9][10][11] or C-Ag(I)-C [12,13], respectively). A variety of artificial ligand-type nucleobases have been developed so as to form metal-mediated base pairs with various metal ions including Mn(II), Ni(II), Cu(II), Pd(II), or Ag(I) ions [1].…”