7UDP

Crystal structure of COQ8A-CA157 inhibitor complex in space group C2

Summary for 7UDP

• Entry DOI: 10.2210/pdb7udp/pdb
• Descriptor: Atypical kinase COQ8A, mitochondrial, 4-[(3,4,5-trimethoxyphenyl)amino]quinoline-7-carbonitrile (3 entities in total)
• Functional Keywords: coq biosynthesis, kinase-like, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 45583.32

Authors

Bingman, C.A.,Murray, N.,Smith, R.W.,Pagliarini, D.J. (deposition date: 2022-03-20, release date: 2023-01-18, Last modification date: 2023-10-25)

Primary citation

Murray, N.H.,Asquith, C.R.M.,Fang, Z.,East, M.P.,Ptak, N.,Smith, R.W.,Vasta, J.D.,Zimprich, C.A.,Corona, C.R.,Robers, M.B.,Johnson, G.L.,Bingman, C.A.,Pagliarini, D.J.
Small-molecule inhibition of the archetypal UbiB protein COQ8.
Nat.Chem.Biol., 19:230-238, 2023

PubMed Abstract: Small-molecule tools have enabled mechanistic investigations and therapeutic targeting of the protein kinase-like (PKL) superfamily. However, such tools are still lacking for many PKL members, including the highly conserved and disease-related UbiB family. Here, we sought to develop and characterize an inhibitor for the archetypal UbiB member COQ8, whose function is essential for coenzyme Q (CoQ) biosynthesis. Guided by crystallography, activity assays and cellular CoQ measurements, we repurposed the 4-anilinoquinoline scaffold to selectively inhibit human COQ8A in cells. Our chemical tool promises to lend mechanistic insights into the activities of these widespread and understudied proteins and to offer potential therapeutic strategies for human diseases connected to their dysfunction.

PubMed: 36302899
DOI: 10.1038/s41589-022-01168-3

Experimental method

X-RAY DIFFRACTION (2.01 Å)