Ho C K, Shuman S
Molecular Biology Program, Sloan-Kettering Institute, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3050-5. doi: 10.1073/pnas.061636198. Epub 2001 Mar 6.
Analysis of the mRNA capping apparatus of the malaria parasite Plasmodium falciparum illuminates an evolutionary connection to fungi rather than metazoans. We show that P. falciparum encodes separate RNA guanylyltransferase (Pgt1) and RNA triphosphatase (Prt1) enzymes and that the triphosphatase component is a member of the fungal/viral family of metal-dependent phosphohydrolases, which are structurally and mechanistically unrelated to the cysteine-phosphatase-type RNA triphosphatases found in metazoans and plants. These results highlight the potential for discovery of mechanism-based antimalarial drugs designed to specifically block the capping of Plasmodium mRNAs. A simple heuristic scheme of eukaryotic phylogeny is suggested based on the structure and physical linkage of the triphosphatase and guanylyltransferase enzymes that catalyze cap formation.
对疟原虫恶性疟原虫的mRNA加帽装置的分析揭示了其与真菌而非后生动物的进化联系。我们发现恶性疟原虫编码单独的RNA鸟苷酸转移酶(Pgt1)和RNA三磷酸酶(Prt1),并且三磷酸酶成分是金属依赖性磷酸水解酶的真菌/病毒家族的成员,其在结构和机制上与后生动物和植物中发现的半胱氨酸磷酸酶型RNA三磷酸酶无关。这些结果突出了发现基于机制的抗疟药物的潜力,这些药物旨在特异性阻断疟原虫mRNA的加帽。基于催化帽形成的三磷酸酶和鸟苷酸转移酶的结构和物理联系,提出了一种简单的真核生物系统发育启发式方案。