Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 508-513 |
| Number of pages | 7 |
| Journal | Nature Chemical Biology |
| Volume | 13 |
| Issue number | 5 |
| Early online date | 6 Mar 2017 |
| DOIs | |
| Publication status | Published - May 2017 |
Fingerprint
Keywords
- RNA catalysis
- metal ions
- RNA structure
- X-ray crysallography
Cite this
}
The structure of a nucleolytic ribozyme that employs a catalytic metal ion. / Liu, Yijin; Wilson, Timothy; Lilley, David (Lead / Corresponding author).
In: Nature Chemical Biology, Vol. 13, No. 5, 05.2017, p. 508-513.Research output: Contribution to journal › Article
TY - JOUR
T1 - The structure of a nucleolytic ribozyme that employs a catalytic metal ion
AU - Liu, Yijin
AU - Wilson, Timothy
AU - Lilley, David
N1 - Funding: CRUK for program support A18604 (to DMJL), the Wellcome Trust for the in-house diffractometer and ESRF for synchrotron beam time.
PY - 2017/5
Y1 - 2017/5
N2 - The TS ribozyme (originally called twister-sister) is a nucleolytic catalytic RNA. We present a crystal structure of the ribozyme in a pre-reactive conformation. Two co-axial helical stacks are organized by a three-way junction and two tertiary contacts. Five divalent metal ions are directly coordinated to RNA ligands, making important contributions to the RNA architecture. The scissile phosphate lies in a quasi-helical loop region that is organized by a network of hydrogen bonding. A divalent metal ion is directly bound to the nucleobase 5' to the scissile phosphate, with an innersphere water molecule positioned to interact with the O2' nucleophile. The rate of ribozyme cleavage correlated in a log-linear manner with divalent metal ion pKa, consistent with proton transfer in the transition state, and we propose the bound metal ion is a likely general base for the cleavage reaction. Our data indicate that the TS ribozyme functions predominantly as a metalloenzyme.
AB - The TS ribozyme (originally called twister-sister) is a nucleolytic catalytic RNA. We present a crystal structure of the ribozyme in a pre-reactive conformation. Two co-axial helical stacks are organized by a three-way junction and two tertiary contacts. Five divalent metal ions are directly coordinated to RNA ligands, making important contributions to the RNA architecture. The scissile phosphate lies in a quasi-helical loop region that is organized by a network of hydrogen bonding. A divalent metal ion is directly bound to the nucleobase 5' to the scissile phosphate, with an innersphere water molecule positioned to interact with the O2' nucleophile. The rate of ribozyme cleavage correlated in a log-linear manner with divalent metal ion pKa, consistent with proton transfer in the transition state, and we propose the bound metal ion is a likely general base for the cleavage reaction. Our data indicate that the TS ribozyme functions predominantly as a metalloenzyme.
KW - RNA catalysis
KW - metal ions
KW - RNA structure
KW - X-ray crysallography
U2 - 10.1038/nchembio.2333
DO - 10.1038/nchembio.2333
M3 - Article
C2 - 28263963
VL - 13
SP - 508
EP - 513
JO - Nature Chemical Biology
JF - Nature Chemical Biology
SN - 1552-4450
IS - 5
ER -