Leishmania major Expresses a Single Dihydroxyacetone Phosphate Acyltransferase Localized in the Glycosome, Important for Rapid Growth and Survival at High Cell Density and Essential for Virulence*
Leishmania major Expresses a Single Dihydroxyacetone Phosphate Acyltransferase Localized in the Glycosome, Important for Rapid Growth and Survival at High Cell Density and Essential for Virulence*
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大型利什曼原虫表达位于糖体中的单一二羟基丙酮磷酸酰基转移酶，对于高细胞密度下的快速生长和存活很重要，并且对于毒力至关重要*
DOI：
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发表时间：
2006
影响因子：
4.8
通讯作者：
C. Mamoun
中科院分区：
文献类型：
--
作者：
R. Zufferey;C. Mamoun
尽管对人类原生动物寄生虫大利什曼原虫的致病机制的了解取得了很大进展，但对其主要甘油脂合成的最初步骤所涉及的酶和主要前体知之甚少，包括参与毒力的那些。我们以前已经证明，前体3-磷酸甘油的酰化反应的初始步骤对于这种寄生虫的酯和乙醚磷脂的合成并不是必需的。在这里，我们表明利什曼原虫表达单一的酰基转移酶，对前体二羟丙酮磷酸具有高度的特异性，并且在棕榈酰辅酶A存在下表现出最好的活性。我们已经鉴定并鉴定了编码这种活性的LmDAT基因。LmDAT补充了酵母中因失去二羟丙酮磷酸和甘油-3-磷酸酰基转移酶活性而导致的致死性。重组LmDAT的生化性质类似于前鞭毛虫期寄生虫的天然酶。我们发现LmDAT是一种糖体酶，它在Δlmdat/Δlmdat零突变中的缺失导致寄生虫二羟丙酮磷酸酰基转移酶的活性完全丧失。此外，缺乏LmDAT会导致寄生虫在对数生长期的分裂发生重大变化，在稳定期加速细胞死亡，并导致毒力丧失。综上所述，我们的结果表明，LmDAT是主要存在于过氧化体中的唯一的二羟丙酮磷酸酰基转移酶，对生长和生存是重要的，对毒力也是必不可少的。
Despite major advances in the understanding of pathogenesis of the human protozoan parasite Leishmania major, little is known about the enzymes and the primary precursors involved in the initial steps of synthesis of its major glycerolipids including those involved in virulence. We have previously demonstrated that the initial step of acylation of the precursor glycerol 3-phosphate is not essential for the synthesis of ester and ether phospholipids in this parasite. Here we show that Leishmania expresses a single acyltransferase with high specificity for the precursor dihydroxyacetone phosphate and shows the best activity in the presence of palmitoyl-CoA. We have identified and characterized the LmDAT gene encoding this activity. LmDAT complements the lethality resulting from the loss of both dihydroxyacetone phosphate and glycerol-3-phosphate acyltransferase activities in yeast. Recombinant LmDAT exhibits biochemical properties similar to those of the native enzyme of the promastigote stage parasites. We show that LmDAT is a glycosomal enzyme and its loss in a Δlmdat/Δlmdat null mutant results in complete abrogation of the parasite dihydroxyacetone phosphate acyltransferase activity. Furthermore, lack of LmDAT causes a major alteration in parasite division during the logarithmic phase of growth, an accelerated cell death during stationary phase, and loss of virulence. Together, our results demonstrate that LmDAT is the only dihydroxyacetone phosphate acyltransferase of the L. major localized in the peroxisome, important for growth and survival and essential for virulence.
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影响因子：
10.5
作者：
Sommer,JM;Wang,CC
通讯作者：
Wang,CC
DOI：
10.1073/pnas.95.25.14687
发表时间：
1998-12-08
影响因子：
11.1
作者：
Ngô, H;Tschudi, C;Ullu, E
通讯作者：
Ullu, E
从豚鼠肝过氧化物酶体中纯化二羟丙酮磷酸酰基转移酶。
影响因子：
3.9
作者：
Webber,KO;Hajra,AK
通讯作者：
Hajra,AK
影响因子：
14.9
作者：
Miller, CA;Martinat, MA;Hyman, LE
通讯作者：
Hyman, LE