PDBsum entry 3ger

RNA

PDB id: 3ger

Contents

DNA/RNA

Ligands

6GU

ACT

NCO ×12

Waters ×242

PDB id:

3ger

Name:

RNA

Title:

Guanine riboswitch bound to 6-chloroguanine

Structure:

Guanine riboswitch. Chain: a. Engineered: yes

Source:

Synthetic: yes. Other_details: this sequence was engineered based on the guanine riboswitch in the 5'utr of the xpt-pbux gene in bacillus subtilis.

Resolution:

1.70Å R-factor: 0.216 R-free: 0.234

Authors:

S.D.Gilbert,R.T.Batey

Key ref:

S.D.Gilbert et al. (2009). Adaptive ligand binding by the purine riboswitch in the recognition of guanine and adenine analogs. Structure, 17, 857-868. PubMed id: 19523903 DOI: 10.1016/j.str.2009.04.009

Date:

25-Feb-09 Release date: 23-Jun-09

DNA/RNA chain

G-G-A-C-A-U-A-U-A-A-U-C-G-C-G-U-G-G-A-U-A-U-G-G-C-A-C-G-C-A-A-G-U-U-U-C-U-A-C- 67 bases

DOI no: 10.1016/j.str.2009.04.009

Structure 17:857-868 (2009)

PubMed id: 19523903

Adaptive ligand binding by the purine riboswitch in the recognition of guanine and adenine analogs.

S.D.Gilbert, F.E.Reyes, A.L.Edwards, R.T.Batey.

ABSTRACT

Purine riboswitches discriminate between guanine and adenine by at least 10,000-fold based on the identity of a single pyrimidine (Y74) that forms a Watson-Crick base pair with the ligand. To understand how this high degree of specificity for closely related compounds is achieved through simple pairing, we investigated their interaction with purine analogs with varying functional groups at the 2- and 6-positions that have the potential to alter interactions with Y74. Using a combination of crystallographic and calorimetric approaches, we find that binding these purines is often facilitated by either small structural changes in the RNA or tautomeric changes in the ligand. This work also reveals that, along with base pairing, conformational restriction of Y74 significantly contributes to nucleobase selectivity. These results reveal that compounds that exploit the inherent local flexibility within riboswitch binding pockets can alter their ligand specificity.

Selected figure(s)

Figure 1.
Figure 1. Ligand Binding Site of the Purine Riboswitch and Chemicals
(A) Details of hypoxanthine (top, PDB 1U8D) and adenine (bottom, PDB 1Y26) bound to the guanine and adenine riboswitches, respectively. The specificity pyrimidine (C74 or U74, yellow) forms hydrogen bonds (red dashed lines) to the Watson-Crick face of the ligand (pink), whereas U51, U47, and U22 interact with the other faces of the purine nucleobase. Residues are colored according to their strand position in the junction region. Note that the hydrogen bonding pattern for ligand recognition is identical.
(B) Chemical structures of purine derivatives characterized in this study.

Figure 5.
Figure 5. 6-Position Derivatives Complexed to an Adenine Binding RNA
(A) Structure of 6ClG bound to GRA; double arrow represents a potential halogen bond between the chloro group and U74.
(B) Binding pocket of the 6OMeG:GRA complex; arrow denotes a long hydrogen bond (3.5 Å) between N1(6OMeG) and N3(U74).
(C) Superposition of structures of the wild-type hypoxanthine:GR complex (red), 6ClG:GRA (blue), and 6OMeG:GRA (green). Most atoms in each structure superimpose well, except for a minor repulsion between the ligand and U74 in the 6OMeG:GRA complex to accommodate the methyl group at the Watson-Crick interface.

The above figures are reprinted by permission from Cell Press: Structure (2009, 17, 857-868) copyright 2009.

Figures were selected by an automated process.