Crystals of peptide deformylase from Plasmodium falciparum reveal critical characteristics of the active site for drug design.
Crystals of peptide deformylase from Plasmodium falciparum reveal critical characteristics of the active site for drug design.
复制标题
来自恶性疟原虫的肽去甲酰基酶晶体揭示了药物设计活性位点的关键特征。
DOI：
10.1016/s0969-2126(02)00719-0
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Hol,WimGJ
中科院分区：
文献类型：
--
作者：
Kumar,Abhinav;Nguyen,KietT;Srivathsan,Sumant;Ornstein,Brad;Turley,Stewart;Hirsh,Irwin;Pei,Dehua;Hol,WimGJ
肽脱甲酰基酶催化细菌中新合成的蛋白质的氨基末端fMet残基的脱甲酰基反应，并且最有可能在恶性疟原虫中，并且因此已被鉴定为潜在的抗菌和抗疟疾药物靶标。P.恶性疟原虫肽脱甲酰基酶在2.8 μ m分辨率下测定，每个不对称单位有10个亚基，与细菌酶相似，具有参与催化的残基、结合金属离子的位置和在两种酶之间结构上保守的催化重要的水。然而，底物结合区域的关键差异解释了E的亲和力差。Colideformylase inhibitors and substrates towards the Plasmodiumenzyme.疟原虫的结构为设计新型抗疟药提供了指导。
Peptide deformylase catalyzes the deformylation reaction of the amino terminal fMet residue of newly synthesized proteins in bacteria, and most likely inPlasmodium falciparum, and has therefore been identified as a potential antibacterial and antimalarial drug target. The structure ofP. falciparumpeptide deformylase, determined at 2.8 Å resolution with ten subunits per asymmetric unit, is similar to the bacterial enzyme with the residues involved in catalysis, the position of the bound metal ion, and a catalytically important water structurally conserved between the two enzymes. However, critical differences in the substrate binding region explain the poor affinity ofE. colideformylase inhibitors and substrates toward thePlasmodiumenzyme. ThePlasmodiumstructure serves as a guide for designing novel antimalarials.