Shankar Jay, Tuteja Renu
International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India.
Gene. 2008 Mar 15;410(2):223-33. doi: 10.1016/j.gene.2007.12.015. Epub 2007 Dec 27.
Malaria caused by the mosquito-transmitted parasite Plasmodium is the cause of enormous number of deaths every year in the tropical and subtropical areas of the world. Among four species of Plasmodium, Plasmodium falciparum causes most fatal form of malaria. With time, the parasite has developed insecticide and drug resistance. Newer strategies and advent of novel drug targets are required so as to combat the deadly form of malaria. Helicases is one such class of enzymes which has previously been suggested as potential antiviral and anticancer targets. These enzymes play an essential role in nearly all the nucleic acid metabolic processes, catalyzing the transient opening of the duplex nucleic acids in an NTP-dependent manner. DNA helicases from the PcrA/UvrD/Rep subfamily are important for the survival of the various organisms. Members from this subfamily can be targeted and inhibited by a variety of synthetic compounds. UvrD from this subfamily is the only member present in the P. falciparum genome, which shows no homology with UvrD from human and thus can be considered as a strong potential drug target. In this manuscript we provide an overview of UvrD family of helicases and bioinformatics analysis of UvrD from P. falciparum.
由蚊子传播的疟原虫引起的疟疾每年在世界热带和亚热带地区导致大量死亡。在四种疟原虫中,恶性疟原虫导致最致命的疟疾形式。随着时间的推移,这种寄生虫已产生了杀虫剂和药物抗性。需要新的策略和新型药物靶点的出现,以对抗这种致命的疟疾形式。解旋酶就是这样一类酶,此前已被认为是潜在的抗病毒和抗癌靶点。这些酶在几乎所有核酸代谢过程中都起着至关重要的作用,以依赖NTP的方式催化双链核酸的瞬时打开。来自PcrA/UvrD/Rep亚家族的DNA解旋酶对各种生物体的生存很重要。该亚家族的成员可以被多种合成化合物靶向和抑制。来自这个亚家族的UvrD是恶性疟原虫基因组中唯一存在的成员,它与人类的UvrD没有同源性,因此可以被认为是一个强大的潜在药物靶点。在本手稿中,我们概述了解旋酶的UvrD家族,并对恶性疟原虫的UvrD进行了生物信息学分析。