Inhibitors of pantothenate kinase: novel antibiotics for staphylococcal infections.
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ABSTRACT:
SUBMITTER: Choudhry AE
PROVIDER: S-EPMC155856 | biostudies-literature | 2003 Jun
REPOSITORIES: biostudies-literature
Publications
Inhibitors of pantothenate kinase: novel antibiotics for staphylococcal infections.
Choudhry Anthony E AE Mandichak Tracy L TL Broskey John P JP Egolf Richard W RW Kinsland Cynthia C Begley Tadhg P TP Seefeld Mark A MA Ku Thomas W TW Brown James R JR Zalacain Magdalena M Ratnam Kapila K
Antimicrobial agents and chemotherapy 20030601 6
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. ...[more]
Similar Datasets
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Project description:Coenzyme A is synthesised from pantothenate via five enzyme-mediated steps. The first step is catalysed by pantothenate kinase (PanK). All PanKs characterised to date form homodimers. Many organisms express multiple PanKs. In some cases, these PanKs are not functionally redundant, and some appear to be non-functional. Here, we investigate the PanKs in two pathogenic apicomplexan parasites, Plasmodium falciparum and Toxoplasma gondii. Each of these organisms express two PanK homologues (PanK1 and PanK2). We demonstrate that PfPanK1 and PfPanK2 associate, forming a single, functional PanK complex that includes the multi-functional protein, Pf14-3-3I. Similarly, we demonstrate that TgPanK1 and TgPanK2 form a single complex that possesses PanK activity. Both TgPanK1 and TgPanK2 are essential for T. gondii proliferation, specifically due to their PanK activity. Our study constitutes the first examples of heteromeric PanK complexes in nature and provides an explanation for the presence of multiple PanKs within certain organisms.
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2024-10-24 | GSE273694 | GEO
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