3MY1
Structure of CDK9/cyclinT1 in complex with DRB
Summary for 3MY1
| Entry DOI | 10.2210/pdb3my1/pdb |
| Related | 3BLH 3BLQ 3BLR 3MY5 |
| Descriptor | Cell division protein kinase 9, Cyclin-T1, PHOSPHATE ION, ... (6 entities in total) |
| Functional Keywords | cdk-cyclin complex, phosphorylated, transcription-protein binding-inhibitor complex, transcription/protein binding/inhibitor |
| Biological source | Homo sapiens (human) More |
| Cellular location | Nucleus: P50750 O60563 |
| Total number of polymer chains | 2 |
| Total formula weight | 69048.09 |
| Authors | Baumli, S.,Johnson, L.N. (deposition date: 2010-05-09, release date: 2010-09-29, Last modification date: 2024-10-30) |
| Primary citation | Baumli, S.,Endicott, J.A.,Johnson, L.N. Halogen bonds form the basis for selective P-TEFb inhibition by DRB Chem.Biol., 17:931-936, 2010 Cited by PubMed Abstract: Cdk9, the kinase of the positive transcription elongation factor b, is required for processive transcription elongation by RNA polymerase II. Cdk9 inhibition contributes to the anticancer activity of many Cdk inhibitors under clinical investigation and hence there is interest in selective Cdk9 inhibitors. DRB (5,6-dichlorobenzimidazone-1-β-D-ribofuranoside) is a commonly used reagent for Cdk9 inhibition in cell biology studies. The crystal structures of Cdk9 and Cdk2 in complex with DRB reported here describe the molecular basis for the DRB selectivity toward Cdk9. The DRB chlorine atoms form halogen bonds that are specific for the Cdk9 kinase hinge region. Kinetic and thermodynamic experiments validate the structural findings and implicate the C-terminal residues of Cdk9 in contributing to the affinity for DRB. These results open the possibility to exploit halogen atoms in inhibitor design to specifically target Cdk9. PubMed: 20851342DOI: 10.1016/j.chembiol.2010.07.012 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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