Crystal Structure of a Type III Pantothenate Kinase: Insight into the Mechanism of an Essential Coenzyme A Biosynthetic Enzyme Universally Distributed in Bacteria

摘要: Pantothenate kinase (PanK) catalyzes the first step in five-step universal pathway of coenzyme A (CoA) biosynthesis, a key transformation that generally also regulates intracellular concentration CoA through feedback inhibition. novel PanK protein encoded by gene coaX was recently identified is distinct from previously characterized type I (exemplified Escherichia coli coaA-encoded protein) and II eukaryotic PanKs not inhibited or its thioesters. This III PanK, PanK-III, widely distributed bacterial kingdom accounts for only known many pathogenic species, such as Helicobacter pylori, Bordetella pertussis, Pseudomonas aeruginosa. Here we report crystal structure enzyme Thermotoga maritima (PanK(Tm)), solved at 2.0-A resolution. The PanK(Tm) reveals belong to acetate sugar kinase/heat shock 70/actin (ASKHA) superfamily they retain highly conserved active site motifs common all members this superfamily. Comparative structural analysis configuration mutagenesis three aspartates identify these residues critical PanK-III catalysis. Furthermore, provides an explanation lack inhibition enzyme. Since adopts different fold E. -- which member "P-loop kinase"superfamily finding represents yet another example convergent evolution same biological function ancestor.