Cofactor metabolism and mitochondrial function in malaria parasites
疟原虫的辅因子代谢和线粒体功能
基本信息
- 批准号:10659968
- 负责人:
- 金额:$ 76.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-18 至 2027-07-31
- 项目状态:未结题
- 来源:
- 关键词:AbbreviationsAcetyl Coenzyme AAcyl Carrier ProteinAdoptedAmino AcidsBiochemicalBiologyBloodCaprylatesCellsCellular biologyChemicalsCoenzyme ACoenzymesDataDevelopmentDrug resistanceElementsEnvironmentEnzymesErythrocytesEscherichia coliEukaryotic CellGenesGlycineGoalsHemagglutininHumanIodoacetamideKetoglutarate Dehydrogenase ComplexLife Cycle StagesLigaseLigationLinkMalariaMetabolic PathwayMetabolismMitochondriaMitochondrial ProteinsNuclearNutrientOrganellesOxidation-ReductionParasitesPathway interactionsPlasmodiumPlasmodium falciparumProcessProductionProtein AcetylationProteinsPyrimidineResearchRoleSerumSourceSystemTricarboxylic AcidsWorkasexualauxotrophycofactorforginggenetic approachinsightlipoamidaselipoatenovelnovel therapeutic interventionorotatepyruvate dehydrogenasetransmission processuptake
项目摘要
Plasmodium parasites are responsible for hundreds of millions of malaria cases annually. During the asexual
stages of development in red blood cells, malaria parasites acquire certain nutrients from human serum while
retaining the ability to synthesize others. We are studying an essential enzyme cofactor called lipoate and its
metabolism in Plasmodium falciparum. Our studies demonstrate that erythrocytic stage parasites are
auxotrophic for lipoate, even though they contain a metabolic pathway to synthesize this cofactor. Proteins in
the apicoplast organelle rely on lipoate synthesis while proteins in the parasite mitochondrion rely on
scavenging and cannot obtain lipoate synthesized in the apicoplast. The proposed studies are focused on two
aspects of lipoate scavenging and employ a combination of biochemical, cell biology and genetic approaches.
Our first aim is to define the essentail roles of lipoate-dependent proteins and identify the factors required to
support these activities in the parasite mitochondrion. Our second aim will probe the mechanism of lipoate
uptake and attachment to mitochondrial proteins in order to understand how, when and why this process is
gated by redox potential. These studies will forge a detailed link between the lipoate attachment enzymes and
their protein substrates. By virtue of relying on a host nutrient, these proteins represent a vulnerable aspect of
parasite biology which could be targeted at several levels.
疟原虫每年造成数亿例疟疾病例。在无性恋期间
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Manuel Llinas其他文献
Manuel Llinas的其他文献
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{{ truncateString('Manuel Llinas', 18)}}的其他基金
Discovering resistance-resistant antimalarial drug target
发现耐药性抗疟药物靶点
- 批准号:
10741535 - 财政年份:2023
- 资助金额:
$ 76.06万 - 项目类别:
Structure of Malaria Parasite RNA polymerase
疟疾寄生虫 RNA 聚合酶的结构
- 批准号:
10433276 - 财政年份:2022
- 资助金额:
$ 76.06万 - 项目类别:
Structure of Malaria Parasite RNA polymerase
疟疾寄生虫 RNA 聚合酶的结构
- 批准号:
10552645 - 财政年份:2022
- 资助金额:
$ 76.06万 - 项目类别:
Dissecting RNA Regulation During Malaria Parasite Sexual Development
解析疟原虫性发育过程中的 RNA 调控
- 批准号:
9375224 - 财政年份:2017
- 资助金额:
$ 76.06万 - 项目类别:
Dissecting the role of ApiAP2 proteins in transcriptional regulation during Plasmodium falciparum development
剖析 ApiAP2 蛋白在恶性疟原虫发育过程中转录调控中的作用
- 批准号:
9271152 - 财政年份:2016
- 资助金额:
$ 76.06万 - 项目类别:
Dissecting the role of ApiAP2 proteins in transcriptional regulation during Plasmodium falciparum development
剖析 ApiAP2 蛋白在恶性疟原虫发育过程中转录调控中的作用
- 批准号:
9913444 - 财政年份:2016
- 资助金额:
$ 76.06万 - 项目类别:
Dissecting the role of ApiAP2 proteins in transcriptional regulation during Plasmodium falciparum development
剖析 ApiAP2 蛋白在恶性疟原虫发育过程中转录调控中的作用
- 批准号:
9158624 - 财政年份:2016
- 资助金额:
$ 76.06万 - 项目类别:
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