3MK6

Substrate and Inhibitor Binding to Pank

Summary for 3MK6

• Entry DOI: 10.2210/pdb3mk6/pdb
• Related: 2I7P
• Descriptor: Pantothenate kinase 3, ACETYL COENZYME *A, GLYCEROL, ... (4 entities in total)
• Functional Keywords: pank, inhibitor, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q9H999
• Total number of polymer chains: 4
• Total formula weight: 170620.35

Authors

Yun, M.-K.,White, S.W. (deposition date: 2010-04-14, release date: 2010-09-15, Last modification date: 2023-09-06)

Primary citation

Leonardi, R.,Zhang, Y.M.,Yun, M.K.,Zhou, R.,Zeng, F.Y.,Lin, W.,Cui, J.,Chen, T.,Rock, C.O.,White, S.W.,Jackowski, S.
Modulation of Pantothenate Kinase 3 Activity by Small Molecules that Interact with the Substrate/Allosteric Regulatory Domain.
Chem.Biol., 17:892-902, 2010

PubMed Abstract: Pantothenate kinase (PanK) catalyzes the rate-controlling step in coenzyme A (CoA) biosynthesis. PanK3 is stringently regulated by acetyl-CoA and uses an ordered kinetic mechanism with ATP as the leading substrate. Biochemical analysis of site-directed mutants indicates that pantothenate binds in a tunnel adjacent to the active site that is occupied by the pantothenate moiety of the acetyl-CoA regulator in the PanK3acetyl-CoA binary complex. A high-throughput screen for PanK3 inhibitors and activators was applied to a bioactive compound library. Thiazolidinediones, sulfonylureas and steroids were inhibitors, and fatty acyl-amides and tamoxifen were activators. The PanK3 activators and inhibitors either stimulated or repressed CoA biosynthesis in HepG2/C3A cells. The flexible allosteric acetyl-CoA regulatory domain of PanK3 also binds the substrates, pantothenate and pantetheine, and small molecule inhibitors and activators to modulate PanK3 activity.

PubMed: 20797618
DOI: 10.1016/j.chembiol.2010.06.006

Experimental method

X-RAY DIFFRACTION (1.98 Å)