22RD

High-resolution cryo-EM structure of human Polo-like kinase 1 in complex with onvansertib

Summary for 22RD

• Entry DOI: 10.2210/pdb22rd/pdb
• EMDB information: 68616
• Descriptor: Serine/threonine-protein kinase PLK1, 1-(2-HYDROXYETHYL)-8-[[5-(4-METHYLPIPERAZIN-1-YL)-2-(TRIFLUOROMETHOXY)PHENYL]AMINO]-4,5-DIHYDROPYRIMIDO[5,4-G]INDAZOLE-3-CARBOXAMIDE (2 entities in total)
• Functional Keywords: small protein-ligand complex, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 38013.14

Authors

Park, K.,Yoo, Y.,Jeon, H.,Choi, K.,Kwon, E.,Lim, H.,Kim, D.Y.,No, K.T. (deposition date: 2026-01-21, release date: 2026-04-29)

Primary citation

Park, K.,Yoo, Y.,Jeon, H.,Choi, K.,Kim, H.,Kwon, E.,Lim, H.H.,Kim, D.Y.,No, K.T.
High-resolution cryo-EM structures of small protein-ligand complexes near the theoretical size limit.
Nat Commun, 2026

PubMed Abstract: Cryo-electron microscopy (cryo-EM) is a widely used technique for determining macromolecular structures at near-atomic resolution. The theoretical lower limit of particle sizes suitable for cryo-EM structural analysis is estimated to be 38 kDa; typical constraints involve factors such as image contrast and particle alignment accuracy. In this study, we present cryo-EM structures of two protein-ligand complexes near this lower size threshold. First, the structure of the maltose-binding protein complexed with maltose, with a structurally ordered mass of 40.8 kDa, was determined at a resolution of 2.4 Å; both the maltose and water molecules were clearly identified in this structure. The second structure was the kinase domain of human PLK1 complexed with onvansertib, with a structurally ordered mass of 31.6 kDa, below the theoretical 38 kDa limit; this domain was determined at a resolution of 3.4 Å using a gold-supported grid in the presence of β-octyl-glucoside. The density map clearly shows the backbone of PLK1 secondary structure, and the onvansertib. These results demonstrate that cryo-EM can be effectively employed to determine structures of small proteins or domains, and to perform structure-based drug screening for small proteins, without requiring structural fiducials for particle alignment.

PubMed: 41980966
DOI: 10.1038/s41467-026-71934-7

Experimental method

ELECTRON MICROSCOPY (3.38 Å)