title: Structural insights into a key carotenogenesis related enzyme phytoene synthase of P. falciparum: a novel drug target for malaria.
abstract: Carotenoids represent a diverse group of pigments derived from the common isoprenoid precursors and fulfill a variety of critical functions in plants and animals. Phytoene synthase (PSY), a transferase enzyme that catalyzes the first specific step in carotenoid biosynthesis plays a central role in the regulation of a number of essential functions mediated via carotenoids. PSYs have been deeply investigated in plants, bacteria and algae however in apicomplexans it is poorly studied. In an effort to characterize PSY in apicomplexans especially the malaria parasite Plasmodium falciparum (P. falciparum), a detailed bioinformatics analysis is undertaken. We have analysed the Phylogenetic relationship of PSY also referred to as octaprenyl pyrophosphate synthase (OPPS) in P. falciparum with other taxonomic groups. Further, we in silico characterized the secondary and tertiary structures of P. falciparum PSY/OPPS and compared the tertiary structures with crystal structure of Thermotoga maritima (T. maritima) OPPS. Our results evidenced the resemblance of P. falciparum PSY with the active site of T. maritima OPPS. Interestingly, the comparative structural analysis revealed an unconserved unique loop in P. falciparum OPPS/PSY. Such structural insights might contribute novel accessory functions to the protein thus, offering potential drug targets.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067 India.|Department of Biotechnology, Jamia Hamdard, Hamdard Nagar, New Delhi, 110062 India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Shiv Nadar University, Gautam Buddha Nagar, 201314 UP India.
authors.forename: Vijeta
authors.initials: V
authors.lastname: Sharma
authors.affiliation: National Centre for Cell Science, NCCS Complex, Pune, 411007 India.
authors.forename: Swastik
authors.initials: S
authors.lastname: Phulera
authors.affiliation: Department of Biotechnology, Jamia Hamdard, Hamdard Nagar, New Delhi, 110062 India.
authors.forename: M Z
authors.initials: MZ
authors.lastname: Abdin
authors.affiliation: Shiv Nadar University, Gautam Buddha Nagar, 201314 UP India.
authors.forename: R
authors.initials: R
authors.lastname: Ayana
authors.affiliation: Shiv Nadar University, Gautam Buddha Nagar, 201314 UP India.
authors.forename: Shailja
authors.initials: S
authors.lastname: Singh
keywords: Apicomplexa; Carotenoid biosynthesis; Isoprenoid; OPPS; PSY; Phytoene; Plasmodium falciparum