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Toxoplasma gondii serine hydrolases regulate parasite lipid mobilization during growth and replication within the host.
- Source :
-
Cell chemical biology [Cell Chem Biol] 2021 Oct 21; Vol. 28 (10), pp. 1501-1513.e5. Date of Electronic Publication: 2021 May 26. - Publication Year :
- 2021
-
Abstract
- The intracellular protozoan parasite Toxoplasma gondii must scavenge cholesterol and other lipids from the host to facilitate intracellular growth and replication. Enzymes responsible for neutral lipid synthesis have been identified but there is no evidence for enzymes that catalyze lipolysis of cholesterol esters and esterified lipids. Here, we characterize several T. gondii serine hydrolases with esterase and thioesterase activities that were previously thought to be depalmitoylating enzymes. We find they do not cleave palmitoyl thiol esters but rather hydrolyze short-chain lipid esters. Deletion of one of the hydrolases results in alterations in levels of multiple lipids species. We also identify small-molecule inhibitors of these hydrolases and show that treatment of parasites results in phenotypic defects reminiscent of parasites exposed to excess cholesterol or oleic acid. Together, these data characterize enzymes necessary for processing lipids critical for infection and highlight the potential for targeting parasite hydrolases for therapeutic applications.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Catalytic Domain
Hydrolysis
Kinetics
Phylogeny
Protozoan Proteins classification
Protozoan Proteins genetics
Recombinant Proteins biosynthesis
Recombinant Proteins chemistry
Recombinant Proteins isolation & purification
Sequence Alignment
Serine Endopeptidases classification
Serine Endopeptidases genetics
Small Molecule Libraries chemistry
Small Molecule Libraries metabolism
Substrate Specificity
Toxoplasma growth & development
Toxoplasma physiology
Lipid Metabolism physiology
Protozoan Proteins metabolism
Serine Endopeptidases metabolism
Toxoplasma enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 2451-9448
- Volume :
- 28
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cell chemical biology
- Publication Type :
- Academic Journal
- Accession number :
- 34043961
- Full Text :
- https://doi.org/10.1016/j.chembiol.2021.05.001