title: Structure of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase in complex with the feedback inhibitor CoA reveals only one active-site conformation.
abstract: Phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate step in the coenzyme A (CoA) biosynthetic pathway, reversibly transferring an adenylyl group from ATP to 4'-phosphopantetheine to form dephosphocoenzyme A (dPCoA). To complement recent biochemical and structural studies on Mycobacterium tuberculosis PPAT (MtPPAT) and to provide further insight into the feedback regulation of MtPPAT by CoA, the X-ray crystal structure of the MtPPAT enzyme in complex with CoA was determined to 2.11 Å resolution. Unlike previous X-ray crystal structures of PPAT-CoA complexes from other bacteria, which showed two distinct CoA conformations bound to the active site, only one conformation of CoA is observed in the MtPPAT-CoA complex.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: T
authors.initials: T
authors.lastname: Wubben
authors.forename: A D
authors.initials: AD
authors.lastname: Mesecar
mesh_terms: D020134:Catalytic Domain; D003065:Coenzyme A / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D009713:Nucleotidyltransferases / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D040681:Structural Homology, Protein
chemical_list: D008024:Ligands; D009713:Nucleotidyltransferases; C022315:pantetheine-phosphate adenylyltransferase; D003065:Coenzyme A