Involvement of delta-aminolaevulinate synthase encoded by the parasite gene in de novo haem synthesis by Plasmodium falciparum.

Involvement of delta-aminolaevulinate synthase encoded by the parasite gene in de novo haem synthesis by Plasmodium falciparum.
复制标题

寄生虫基因编码的δ-氨基乙酰丙酸合酶参与恶性疟原虫从头合成血红素。

DOI:
--
复制
发表时间:
2002
影响因子:
4.1
通讯作者:
Govindarajan Padmanaban
Govindarajan Padmanaban
中科院分区:
生物学3区
文献类型:
--
作者:
S. Varadharajan;S. Dhanasekaran;ZQ Bonday;P. Rangarajan;Govindarajan Padmanaban

文献摘要

参考文献

被引文献

相似文献

疟原虫可以合成新生血红素。本研究采用逆转录酶链式反应(PCR)对疟原虫δ -氨酰戊酸合成酶(Pf ALAS)基因mRNA的表达进行了研究,利用大肠杆菌中表达的重组蛋白抗体对其进行了蛋白表达,并在培养的恶性疟原虫中测定了ALAS酶的活性。该基因在红细胞内寄生虫生长的所有阶段都有表达,在滋养体阶段有少量表达。红细胞ALAS抗体不会与寄生虫酶发生交叉反应,反之亦然。乙醇胺能抑制重组酶的活性,乙醇胺能抑制恶性疟原虫血红素的合成和培养物的生长。寄生虫ALAS定位于线粒体中,并在无细胞输入试验中被证明可以进入线粒体。进口被封锁了。基于这些结果,我们得出以下结论:PfALAS具有明显的免疫特性和抑制剂特异性,因此是一个药物靶点。疟原虫通过线粒体/细胞质伙伴关系合成血红素,鉴于疟原虫中存在可能能够独立合成血红素的顶质体,这一发现具有重要意义。pfalas基因对寄生虫血红素合成和生存具有重要的功能。
The malaria parasite can synthesize haem de novo. In the present study, the expression of the parasite gene for delta-aminolaevulinate synthase (Pf ALAS ) has been studied by reverse transcriptase PCR analysis of the mRNA, protein expression using antibodies to the recombinant protein expressed in Escherichia coli and assay of ALAS enzyme activity in Plasmodium falciparum in culture. The gene is expressed through all stages of intra-erythrocytic parasite growth, with a small increase during the trophozoite stage. Antibodies to the erythrocyte ALAS do not cross-react with the parasite enzyme and vice versa. The recombinant enzyme activity is inhibited by ethanolamine and the latter inhibits haem synthesis in P. falciparum and growth in culture. The parasite ALAS is localized in the mitochondrion and its import into mitochondria in a cell-free import assay has been demonstrated. The import is blocked by haemin. On the basis of these results, the following conclusions are arrived at: PfALAS has distinct immunological identity and inhibitor specificity and is therefore a drug target. The malaria parasite synthesizes haem through the mitochondrion/cytosol partnership, and this assumes significance in light of the presence of apicoplasts in the parasite that may be capable of independent haem synthesis. The Pf ALAS gene is functional and vital for parasite haem synthesis and parasite survival.
恶性疟原虫 Hsp 60 的分子特征和超微结构定位。
DOI: 10.1016/s0166-6851(97)00081-9
发表时间: 1997
影响因子: 1.5
作者:
Das,A;Syin,C;Fujioka,H;Zheng,H;Goldman,N;Aikawa,M;Kumar,N
通讯作者: Kumar,N
DOI: --
发表时间: 1993
期刊: The Journal of biological chemistry
影响因子: --
作者:
Ferreira,GC;Dailey,HA
通讯作者: Dailey,HA