title: Structure-based binding between protein farnesyl transferase and PRL-PTP of malaria parasite: an interaction study of prenylation process in Plasmodium.
abstract: Protein prenylation is a post-translational modification critical for many cellular processes such as DNA replication, signaling, and trafficking. It is mediated by protein farnesyltransferase by recognizing 'CAAX' motif on protein substrate. Plasmodium falciparum also possesses many such proteins with 'CAAX' motif, involved in various pathways of the parasite. The interaction studies of PfPFT with its substrate were carried out using synthetic peptides but not with full protein. Therefore, in this study, we have modeled both PfPFT and its substrate protein tyrosine phosphatase (PfPRL-PTP) followed by interaction studies using protein-protein docking and molecular dynamics simulation. Our findings provided a clear picture of interactions at atomic level between prenyltransferase and its protein substrate. We are assured that this piece of information can be extended to many other proteins of parasite containing 'CAAX' motif and that it may also lead to the development of anti-malarials based on the inhibition of prenylation-dependent pathways of parasite..
authors.affiliation: a Department of Biotechnology , Central University of Rajasthan , NH-8, Bandarsindri , Rajasthan 305801 , India.
authors.forename: Rani
authors.initials: R
authors.lastname: Soni
authors.affiliation: a Department of Biotechnology , Central University of Rajasthan , NH-8, Bandarsindri , Rajasthan 305801 , India.
authors.forename: Drista
authors.initials: D
authors.lastname: Sharma
authors.affiliation: a Department of Biotechnology , Central University of Rajasthan , NH-8, Bandarsindri , Rajasthan 305801 , India.
authors.forename: Sachin
authors.initials: S
authors.lastname: Patel
authors.affiliation: a Department of Biotechnology , Central University of Rajasthan , NH-8, Bandarsindri , Rajasthan 305801 , India.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Sharma
authors.affiliation: a Department of Biotechnology , Central University of Rajasthan , NH-8, Bandarsindri , Rajasthan 305801 , India.
authors.forename: Tarun Kumar
authors.initials: TK
authors.lastname: Bhatt
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010961:Plasmodium / Q000201:enzymology*; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D015800:Protozoan Proteins; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase
keywords: CAAX motif; Plasmodium falciparum; anti-malarials; docking; molecular dynamics simulation; p.falciparum farnesyl transferase(pfPFT); prenylation; protein tyrosine phosphatase(PTP)