Triglia T, Cowman A F
Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7149-53. doi: 10.1073/pnas.91.15.7149.
The enzyme dihydropteroate synthetase (DHPS) from Plasmodium falciparum is involved in the mechanism of action of the sulfone/sulfonamide group of drugs. We describe the cloning and sequencing of the gene encoding the P. falciparum DHPS enzyme and show that it is a bifunctional enzyme that includes dihydro-6-hydroxymethylpterin pyrophosphokinase (PPPK) at the N terminus of DHPS. The gene encodes a putative protein of 83 kDa that contains two domains that are homologous with the DHPS and PPPK enzymes of other organisms. The PPPK-DHPS gene is encoded on chromosome 8 and has two introns. An antibody raised to the PPPK region of the protein was found to recognize a 68-kDa protein that is expressed throughout the asexual life cycle of the parasite. We have determined the sequence of the DHPS portion of the gene from sulfadoxine-sensitive and -resistant P. falciparum clones and identified sequence differences that may have a role in sulfone/sulfonamide resistance.
恶性疟原虫的二氢蝶酸合酶（DHPS）参与了砜类/磺胺类药物的作用机制。我们描述了编码恶性疟原虫DHPS酶的基因的克隆和测序，并表明它是一种双功能酶，在DHPS的N端包含二氢-6-羟甲基蝶呤焦磷酸激酶（PPPK）。该基因编码一个推定的83 kDa蛋白质，其包含两个与其他生物体的DHPS和PPPK酶同源的结构域。PPPK-DHPS基因位于8号染色体上，有两个内含子。发现针对该蛋白质PPPK区域产生的抗体可识别一种在寄生虫的无性生命周期中均有表达的68 kDa蛋白质。我们已经确定了来自对磺胺多辛敏感和耐药的恶性疟原虫克隆的该基因DHPS部分的序列，并鉴定出了可能与砜类/磺胺类耐药性有关的序列差异。
