9PDG
Three-dimensional structure of kinase inhibitor Palbociclib-HIV TAR complex
Summary for 9PDG
| Entry DOI | 10.2210/pdb9pdg/pdb |
| NMR Information | BMRB: 31259 |
| Descriptor | RNA (29-MER), 6-ACETYL-8-CYCLOPENTYL-5-METHYL-2-[(5-PIPERAZIN-1-YLPYRIDIN-2-YL)AMINO]PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE (2 entities in total) |
| Functional Keywords | palbociclib, complex, hiv-1 tar, rna, small molecule-rna complex |
| Biological source | synthetic construct |
| Total number of polymer chains | 1 |
| Total formula weight | 9757.10 |
| Authors | Ramireddy, R.R.,Vidadala, V.N.,Chaubey, B.,Olsen, G.L.,Varani, G. (deposition date: 2025-06-30, release date: 2026-02-04, Last modification date: 2026-04-08) |
| Primary citation | Ramireddy, R.R.,Vidalala, V.,Chaubey, B.,Olsen, G.L.,Varani, G. Three-dimensional structure of the palbociclib-HIV TAR complex. Nucleic Acids Res., 54:-, 2026 Cited by PubMed Abstract: We present the structure of the HIV-1 transactivation response (TAR) element bound to the kinase inhibitor palbociclib, a single-digit nM ligand and low nM inhibitor of assembly of the super elongation complex. The small molecule rearranges the RNA to create a deep binding pocket within a new structure of TAR. It displaces A22 to form an "intermolecular pair" with U40, generating a continuously stacked 11 base-pair helix, which includes three new base triples involving A22 itself and the UCU bulge nucleotides. Mutation of nucleotides within the binding pocket or small modifications of the small molecule that abrogate high-affinity binding also disrupt direct intermolecular contacts or interactions that stabilize the RNA structure required for binding. It is highly unlikely that such an extensive combination of sequence and structural requirements is duplicated anywhere else in the transcriptome and in a functional context. This structure demonstrates that RNA refolding in response to small molecule binding is key both to providing potent and specific interactions and to eliciting a biochemical response. PubMed: 41844361DOI: 10.1093/nar/gkag129 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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