3BEX

Type III pantothenate kinase from Thermotoga maritima complexed with pantothenate

Summary for 3BEX

• Entry DOI: 10.2210/pdb3bex/pdb
• Related: 3BF1 3BF3
• Descriptor: Type III pantothenate kinase, PHOSPHATE ION, PANTOTHENOIC ACID, ... (4 entities in total)
• Functional Keywords: actin-like fold, atp-binding, coenzyme a biosynthesis, cytoplasm, kinase, metal-binding, nucleotide-binding, potassium, transferase
• Biological source: Thermotoga maritima
• Cellular location: Cytoplasm (By similarity): Q9WZY5
• Total number of polymer chains: 6
• Total formula weight: 167069.55

Authors

Yang, K.,Huerta, C.,Strauss, E.,Zhang, H. (deposition date: 2007-11-20, release date: 2008-06-24, Last modification date: 2023-08-30)

Primary citation

Yang, K.,Strauss, E.,Huerta, C.,Zhang, H.
Structural basis for substrate binding and the catalytic mechanism of type III pantothenate kinase.
Biochemistry, 47:1369-1380, 2008

PubMed Abstract: Pantothenate kinase (PanK) catalyzes the first step of the universal five-step coenzyme A (CoA) biosynthetic pathway. The recently characterized type III PanK (PanK-III, encoded by the coaX gene) is distinct in sequence, structure and enzymatic properties from both the long-known bacterial type I PanK (PanK-I, exemplified by the Escherichia coli CoaA protein) and the predominantly eukaryotic type II PanK (PanK-II). PanK-III enzymes have an unusually high Km for ATP, are resistant to feedback inhibition by CoA, and are unable to utilize the N-alkylpantothenamide family of pantothenate analogues as alternative substrates, thus making type III PanK ineffective in generating CoA analogues as antimetabolites in vivo. Previously, we reported the crystal structure of the PanK-III from Thermotoga maritima and identified it as a member of the "acetate and sugar kinase/heat shock protein 70/actin" (ASKHA) superfamily. Here we report the crystal structures of the same PanK-III in complex with one of its substrates (pantothenate), its product (phosphopantothenate) as well as a ternary complex structure of PanK-III with pantothenate and ADP. These results are combined with isothermal titration calorimetry experiments to present a detailed structural and thermodynamic characterization of the interactions between PanK-III and its substrates ATP and pantothenate. Comparison of substrate binding and catalytic sites of PanK-III with that of eukaryotic PanK-II revealed drastic differences in the binding modes for both ATP and pantothenate substrates, and suggests that these differences may be exploited in the development of new inhibitors specifically targeting PanK-III.

PubMed: 18186650
DOI: 10.1021/bi7018578

Experimental method

X-RAY DIFFRACTION (1.51 Å)