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A novel lipoate attachment enzyme is shared by Plasmodium and Chlamydia species
Author(s) -
Afanador Gustavo A.,
Guerra Alfredo J.,
Swift Russell P.,
Rodriguez Ryan E.,
Bartee David,
Matthews Krista A.,
Schön Arne,
Freire Ernesto,
Freel Meyers Caren L.,
Prigge Sean T.
Publication year - 2017
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13776
Subject(s) - biology , dna ligase , enzyme , biochemistry , cofactor , microbiology and biotechnology , intracellular parasite , intracellular
Summary Lipoate is an essential cofactor for enzymes that are important for central metabolism and other processes. In malaria parasites, scavenged lipoate from the human host is required for survival. The Plasmodium falciparum mitochondrion contains two enzymes ( Pf LipL1 and Pf LipL2) that are responsible for activating mitochondrial proteins through the covalent attachment of lipoate (lipoylation). Lipoylation occurs via a novel redox‐gated mechanism that remains poorly understood. We show that Pf LipL1 functions as a redox switch that determines which downstream proteins will be activated. Based on the lipoate redox state, Pf LipL1 either functions as a canonical lipoate ligase or as a lipoate activating enzyme which works in conjunction with Pf LipL2. We demonstrate that Pf LipL2 is a lipoyltransferase and is a member of a novel clade of lipoate attachment enzymes. We show that a LipL2 enzyme from Chlamydia trachomatis has similar activity, demonstrating conservation between intracellular pathogens from different phylogenetic kingdoms and supporting the hypothesis that an early ancestor of malaria parasites once contained a chlamydial endosymbiont. Redox‐dependent lipoylation may regulate processes such as central metabolism and oxidative defense pathways.