Inhibitors of pantothenate kinase: novel antibiotics for staphylococcal infections

Anthony E Choudhry; Tracy L Mandichak; John P Broskey; Richard W Egolf; Cynthia Kinsland; Tadhg P Begley; Mark A Seefeld; Thomas W Ku; James R Brown; Magdalena Zalacain; Kapila Ratnam

doi:10.1128/AAC.47.6.2051-2055.2003

Inhibitors of pantothenate kinase: novel antibiotics for staphylococcal infections

Antimicrob Agents Chemother. 2003 Jun;47(6):2051-5. doi: 10.1128/AAC.47.6.2051-2055.2003.

Authors

Anthony E Choudhry¹, Tracy L Mandichak, John P Broskey, Richard W Egolf, Cynthia Kinsland, Tadhg P Begley, Mark A Seefeld, Thomas W Ku, James R Brown, Magdalena Zalacain, Kapila Ratnam

Affiliation

¹ Microbial, Musculoskeletal and Proliferative Diseases and Bioinformatics, GlaxoSmithKline Pharmaceuticals, Collegeville Pennsylvania 19426, USA.

Abstract

Pantothenate kinase (CoaA) catalyzes the first step of the coenzyme A biosynthetic pathway. Here we report the identification of the Staphylococcus aureus coaA gene and characterization of the enzyme. We have also identified a series of low-molecular-weight compounds which are effective inhibitors of S. aureus CoaA.

MeSH terms

Adenosine Triphosphate / metabolism
Amino Acid Sequence
Base Sequence
Cloning, Molecular
Coenzyme A / biosynthesis
DNA, Bacterial / chemistry
DNA, Bacterial / genetics
Enzyme Inhibitors / pharmacology*
Humans
Inhibitory Concentration 50
Kinetics
Microbial Sensitivity Tests
Molecular Sequence Data
Pantothenic Acid / metabolism
Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
Phosphotransferases (Alcohol Group Acceptor) / genetics
Phylogeny
Sequence Alignment
Staphylococcal Infections / drug therapy*
Staphylococcal Infections / microbiology
Staphylococcus aureus / enzymology*
Staphylococcus aureus / genetics
Tumor Cells, Cultured

Substances

DNA, Bacterial
Enzyme Inhibitors
Pantothenic Acid
Adenosine Triphosphate
Phosphotransferases (Alcohol Group Acceptor)
pantothenate kinase
Coenzyme A