更新于：2024-11-01

IPC synthase

更新于：2024-11-01

基本信息

别名

AUR1、Aureobasidin A resistance protein homolog、Inositol phosphorylceramide synthase

+ [1]

简介

Catalyzes the addition of a phosphorylinositol group onto ceramide to form inositol phosphorylceramide, an essential step in sphingolipid biosynthesis.

关联

项与 IPC synthase 相关的药物

Aureobasidin A-based cyclic peptides(AureoGen, Inc.)

靶点

IPC synthase

作用机制

IPC synthase抑制剂

在研机构

Merck Sharp & Dohme Corp. [+1]

原研机构

AureoGen, Inc.

在研适应症

真菌病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

Basifungin

靶点

IPC synthase

作用机制

IPC synthase抑制剂

在研机构-

原研机构

Nippon Kayaku Co., Ltd.

在研适应症-

非在研适应症

真菌病

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 IPC synthase 相关的临床结果

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100 项与 IPC synthase 相关的转化医学

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0 项与 IPC synthase 相关的专利（医药）

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131

项与 IPC synthase 相关的文献（医药）

2024-09-01·iScience

Complex sphingolipid profiling and identification of an inositol-phosphorylceramide synthase in Dictyostelium discoideum

Article

作者: Kol, Matthijs ; Barisch, Caroline ; Eising, Sebastian ; Listian, Stevanus A. ; Fröhlich, Florian ; Holthuis, Joost C.M. ; Walter, Stefan ; Mazur, Anna-Carina ; Ufelmann, Edwin ; Listian, Stevanus A ; Holthuis, Joost C M

Dictyostelium discoideum is a professional phagocyte frequently used to study cellular processes underlying the recognition, engulfment, and infection course of microbial pathogens. Sphingolipids are abundant components of the plasma membrane that bind cholesterol, control membrane properties, participate in signal transmission, and serve as adhesion molecules in recognition processes relevant to immunity and infection. By combining lipidomics with a bioinformatics-based cloning strategy, we show here that D. discoideum produces phosphoinositol-containing sphingolipids with predominantly phytoceramide backbones. Cell-free expression of candidate inositol-phosphorylceramide (IPC) synthases from D. discoideum enabled identification of an enzyme that selectively catalyzes the transfer of phosphoinositol from phosphatidylinositol onto ceramide. The IPC synthase, DdIPCS1, shares multiple sequence motifs with yeast IPC and human sphingomyelin synthases and localizes to the Golgi apparatus as well as the contractile vacuole of D. discoideum. These findings open up important opportunities for exploring a role of sphingolipids in phagocytosis and infection across major evolutionary boundaries.

2024-08-09·ACS Infectious Diseases

Evaluation of the Leishmania Inositol Phosphorylceramide Synthase as a Drug Target Using a Chemical and Genetic Approach

Article

作者: Mantilla, Brian S ; Price, Helen P ; Barrett, Michael P ; Ibarra-Meneses, Ana V ; Van Bocxlaer, Katrien ; Whitfield, Philip D ; Fernandez-Prada, Christopher ; Filipe, Laura N S ; Beaudry, Francis ; Wei, Wenbin ; Burle-Caldas, Gabriela A ; Alpizar-Sosa, Edubiel A ; Dickie, Emily A ; Denny, Paul W ; Zimbres, Flavia M

The lack of effective vaccines and the development of resistance to the current treatments highlight the urgent need for new anti-leishmanials. Sphingolipid metabolism has been proposed as a promising source of Leishmania-specific targets as these lipids are key structural components of the eukaryotic plasma membrane and are involved in distinct cellular events. Inositol phosphorylceramide (IPC) is the primary sphingolipid in the Leishmania species and is the product of a reaction mediated by IPC synthase (IPCS). The antihistamine clemastine fumarate has been identified as an inhibitor of IPCS in L. major and a potent anti-leishmanial in vivo. Here we sought to further examine the target of this compound in the more tractable species L. mexicana, using an approach combining genomic, proteomic, metabolomic and lipidomic technologies, with molecular and biochemical studies. While the data demonstrated that the response to clemastine fumarate was largely conserved, unexpected disturbances beyond sphingolipid metabolism were identified. Furthermore, while deletion of the gene encoding LmxIPCS had little impact in vitro, it did influence clemastine fumarate efficacy and, importantly, in vivo pathogenicity. Together, these data demonstrate that clemastine does inhibit LmxIPCS and cause associated metabolic disturbances, but its primary target may lie elsewhere.

2024-08-01·Journal of Integrative Plant Biology

α1‐COP modulates plasmodesmata function through sphingolipid enzyme regulation

Article

作者: Wu, Shuwei ; Kim, Woe Yoen ; Shon, Jong Cheol ; Son, Geon Hui ; Iswanto, Arya Bagus Boedi ; Liu, Kwang Hyeon ; Kumar, Ritesh ; Kim, Sang Hee ; Kim, Jae-Yean ; Kwak, Youn-Sig ; Vu, Minh Huy ; Kang, Hobin ; Kim, Da-Ran

ABSTRACTCallose, a β‐1,3‐glucan plant cell wall polymer, regulates symplasmic channel size at plasmodesmata (PD) and plays a crucial role in a variety of plant processes. However, elucidating the molecular mechanism of PD callose homeostasis is limited. We screened and identified an Arabidopsis mutant plant with excessive callose deposition at PD and found that the mutated gene was α1‐COP, a member of the coat protein I (COPI) coatomer complex. We report that loss of function of α1‐COP elevates the callose accumulation at PD by affecting subcellular protein localization of callose degradation enzyme PdBG2. This process is linked to the functions of ERH1, an inositol phosphoryl ceramide synthase, and glucosylceramide synthase through physical interactions with the α1‐COP protein. Additionally, the loss of function of α1‐COP alters the subcellular localization of ERH1 and GCS proteins, resulting in a reduction of GlcCers and GlcHCers molecules, which are key sphingolipid (SL) species for lipid raft formation. Our findings suggest that α1‐COP protein, together with SL modifiers controlling lipid raft compositions, regulates the subcellular localization of GPI‐anchored PDBG2 proteins, and hence the callose turnover at PD and symplasmic movement of biomolecules. Our findings provide the first key clue to link the COPI‐mediated intracellular trafficking pathway to the callose‐mediated intercellular signaling pathway through PD.