Pneumocystis S-adenosylmethionine transport: a potential drug target.
Pneumocystis S-adenosylmethionine transport: a potential drug target.
复制标题
肺孢子菌 S-腺苷甲硫氨酸转运：潜在的药物靶点。
DOI：
10.1165/rcmb.2011-0009oc
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发表时间：
2011
影响因子：
6.4
通讯作者：
Merali,Salim
中科院分区：
文献类型：
--
作者：
Perez-Leal,Oscar;Moncada,Camilo;Clarkson,AllenB;Merali,Salim
Pneumocystispneumonia (PCP) is a life-threatening condition in immunosuppressed patients. Current treatments are inadequate, and new drug leads are needed. This fungus depends on its host for S-adenosylmethionine (AdoMet), a critical metabolic intermediate ordinarily synthesized by individual cells as needed.Pneumocystiscontains a gene coding for the AdoMet-synthesizing enzyme methionine ATP transferase (MAT), and the protein is expressed. However, the fungus lacks MAT activity, and infection causes the depletion of host plasma AdoMet. The uptake ofPneumocystisAdoMet was shown to be exquisitely specific, which suggests the transport of AdoMet as a potential drug target. Here we report on the discovery ofPcPET8, aPneumocystisgene with homology to mitochondrial AdoMet transporters. When expressed bySaccharomyces cerevisiae, it locates properly to the mitochondrion and complements a strain ofS. cerevisiaelacking its native mitochondrial AdoMet transporter. The importance of AdoMet transport is demonstrated by the ability of the AdoMet analogue sinefungin to block the uptake ofPneumocystisAdoMet and inhibit growth in culture. BecausePcPET8is likely critical forPneumocystis, the yeast construct has potential as a surrogate for testing compounds againstPneumocystis.
