8TQX

Crystal structure of the Zika virus stem-loop A (SLA) bottom stem

Summary for 8TQX

• Entry DOI: 10.2210/pdb8tqx/pdb
• Descriptor: Zika virus stem-loop A (SLA) bottom stem, MAGNESIUM ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: zika virus, flavivirus, rna structure, stem-loop a, rna
• Biological source: Zika virus
• Total number of polymer chains: 2
• Total formula weight: 12225.67

Authors

Tipo, J.,Gottipati, K.,Choi, K.H. (deposition date: 2023-08-08, release date: 2024-03-06, Last modification date: 2024-05-29)

Primary citation

Tipo, J.,Gottipati, K.,Choi, K.H.
High-resolution RNA tertiary structures in Zika virus stem-loop A for the development of inhibitory small molecules.
Rna, 30:609-623, 2024

PubMed Abstract: Flaviviruses such as Zika (ZIKV) and dengue virus (DENV) are positive-sense RNA viruses belonging to Flaviviridae. The flavivirus genome contains a 5' end stem-loop promoter sequence known as stem-loop A (SLA) that is recognized by the flavivirus polymerase NS5 during viral RNA synthesis and 5' guanosine cap methylation. The crystal structures of ZIKV and DENV SLAs show a well-defined fold, consisting of a bottom stem, side loop, and top stem-loop, providing unique interaction sites for small-molecule inhibitors to disrupt the promoter function. To facilitate identification of small molecule binding sites in flavivirus SLA, we determined high-resolution structures of bottom and top stems of ZIKV SLA, which contain a single U- or G-bulge, respectively. Both bulge nucleotides exhibit multiple orientations, from folded back on the adjacent nucleotide to flipped out of the helix, and are stabilized by stacking or base triple interactions. These structures suggest that even a single unpaired nucleotide can provide flexibility to RNA structures and its conformation is mainly determined by the stabilizing chemical environment. To facilitate discovery of small molecule inhibitors that interfere with the functions of ZIKV SLA, we screened and identified compounds that bind to the bottom and top stems of ZIKV SLA.

PubMed: 38383158
DOI: 10.1261/rna.079796.123

Experimental method

X-RAY DIFFRACTION (2.09 Å)