6WQX

Human PRPK-TPRKB complex

Summary for 6WQX

• Entry DOI: 10.2210/pdb6wqx/pdb
• Descriptor: EKC/KEOPS complex subunit TPRKB, EKC/KEOPS complex subunit TP53RK, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total)
• Functional Keywords: trna modification, kinase, protein binding, protein binding-transferase complex, protein binding/transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 100856.43

Authors

Li, J.,Ma, X.L.,Banerjee, S.,Dong, Z.G. (deposition date: 2020-04-29, release date: 2021-02-17, Last modification date: 2023-10-18)

Primary citation

Li, J.,Ma, X.,Banerjee, S.,Chen, H.,Ma, W.,Bode, A.M.,Dong, Z.
Crystal structure of the human PRPK-TPRKB complex.
Commun Biol, 4:167-167, 2021

PubMed Abstract: Mutations of the p53-related protein kinase (PRPK) and TP53RK-binding protein (TPRKB) cause Galloway-Mowat syndrome (GAMOS) and are found in various human cancers. We have previously shown that small compounds targeting PRPK showed anti-cancer activity against colon and skin cancer. Here we present the 2.53 Å crystal structure of the human PRPK-TPRKB-AMPPNP (adenylyl-imidodiphosphate) complex. The structure reveals details in PRPK-AMPPNP coordination and PRPK-TPRKB interaction. PRPK appears in an active conformation, albeit lacking the conventional kinase activation loop. We constructed a structural model of the human EKC/KEOPS complex, composed of PRPK, TPRKB, OSGEP, LAGE3, and GON7. Disease mutations in PRPK and TPRKB are mapped into the structure, and we show that one mutation, PRPK K238Nfs*2, lost the binding to OSGEP. Our structure also makes the virtual screening possible and paves the way for more rational drug design.

PubMed: 33547416
DOI: 10.1038/s42003-021-01683-4

Experimental method

X-RAY DIFFRACTION (2.53 Å)