6wqx

Publication Abstract from PubMed

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 A 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.

Crystal structure of the human PRPK-TPRKB complex.,Li J, Ma X, Banerjee S, Chen H, Ma W, Bode AM, Dong Z Commun Biol. 2021 Feb 5;4(1):167. doi: 10.1038/s42003-021-01683-4. PMID:33547416^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.