12EZSummary for 12EZ
| Entry DOI | 10.2210/pdb12ez/pdb |
| Descriptor | RIO-type serine/threonine-protein kinase Rio1, 4-amino-7-[5-thio-5-S-(1H-1,2,4-triazol-3-yl)-alpha-L-arabinofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (3 entities in total) |
| Functional Keywords | rio kinase 1, inhibitor, riok1, transferase |
| Biological source | Archaeoglobus fulgidus |
| Total number of polymer chains | 2 |
| Total formula weight | 59788.48 |
| Authors | Hunter, D. (deposition date: 2026-04-01, release date: 2026-08-26, Last modification date: 2026-09-02) |
| Primary citation | Hunter, D.A.,Yu, W.,Puranik, P.,Banerjee, A.,Pozharski, E.,Seraj, N.,Chang, M.,Cooper, J.,Strickland, D.,Dave, V.,LaRonde, N.,MacKerell Jr., A.D.,Weber, D.J. Structure of an inhibitor bound to the catalytically important divalent metal ion site of afRioK1. J.Struct.Biol., 218:108355-108355, 2026 Cited by PubMed Abstract: Rio Kinase 1 (RioK1) is an anti-cancer target for colorectal cancer. In pursuit of selective inhibitors of RioK1, small drug-like molecules were identified using computer-aided drug design (CADD). CADD made use of a 3D crystal structure of human RioK1 bound to ADP/Mg and a fragment-based computational method termed Site-Identification by Ligand Competitive Saturation (SILCS). Compounds identified via SILCS were selected based on predicted binding affinities and were experimentally confirmed to bind a RioK1 homolog from Archaeoglobus fulgidus via biophysical methods. One newly designed scaffold molecule, KPSH02, had its X-ray crystal structure determined in complex with afRioK1. The structure confirmed that KPSH02 occupies the adenine binding region seen in the Toyocamycin-afRioK1 structure, while also occupying the divalent metal-ion site observed in the hsRioK1-ADP structure. This structure thereby provides novel insights that may be exploited for the design of selective RioK1 inhibitors that may be useful in the future for targeting RioK1 in cancer. PubMed: 42595235DOI: 10.1016/j.jsb.2026.108355 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.76 Å) |
Structure validation
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