4PED

Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthes

Summary for 4PED

• Entry DOI: 10.2210/pdb4ped/pdb
• Descriptor: Chaperone activity of bc1 complex-like, mitochondrial, SULFATE ION (3 entities in total)
• Functional Keywords: protein kinase-like, coenzyme q biosynthesis, mitochondrial, membrane associated, structural genomics, psi-biology, mitochondrial protein partnership, mpp, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 46143.50

Authors

Bingman, C.A.,Smith, R.,Joshi, S.,Stefely, J.A.,Reidenbach, A.G.,Ulbrich, A.,Oruganty, O.,Floyd, B.J.,Jochem, A.,Saunders, J.M.,Johnson, I.E.,Wrobel, R.L.,Barber, G.E.,Lee, D.,Li, S.,Kannan, N.,Coon, J.J.,Pagliarini, D.J.,Mitochondrial Protein Partnership (MPP) (deposition date: 2014-04-22, release date: 2014-11-19, Last modification date: 2023-12-27)

Primary citation

Stefely, J.A.,Reidenbach, A.G.,Ulbrich, A.,Oruganty, K.,Floyd, B.J.,Jochem, A.,Saunders, J.M.,Johnson, I.E.,Minogue, C.E.,Wrobel, R.L.,Barber, G.E.,Lee, D.,Li, S.,Kannan, N.,Coon, J.J.,Bingman, C.A.,Pagliarini, D.J.
Mitochondrial ADCK3 Employs an Atypical Protein Kinase-like Fold to Enable Coenzyme Q Biosynthesis.
Mol.Cell, 57:83-94, 2015

PubMed Abstract: The ancient UbiB protein kinase-like family is involved in isoprenoid lipid biosynthesis and is implicated in human diseases, but demonstration of UbiB kinase activity has remained elusive for unknown reasons. Here, we quantitatively define UbiB-specific sequence motifs and reveal their positions within the crystal structure of a UbiB protein, ADCK3. We find that multiple UbiB-specific features are poised to inhibit protein kinase activity, including an N-terminal domain that occupies the typical substrate binding pocket and a unique A-rich loop that limits ATP binding by establishing an unusual selectivity for ADP. A single alanine-to-glycine mutation of this loop flips this coenzyme selectivity and enables autophosphorylation but inhibits coenzyme Q biosynthesis in vivo, demonstrating functional relevance for this unique feature. Our work provides mechanistic insight into UbiB enzyme activity and establishes a molecular foundation for further investigation of how UbiB family proteins affect diseases and diverse biological pathways.

PubMed: 25498144
DOI: 10.1016/j.molcel.2014.11.002

Experimental method

X-RAY DIFFRACTION (1.64 Å)