NTPase and 5'-RNA triphosphatase activities of Chikungunya virus nsP2 protein
Autor(es): Karpe Yogesh A, Aher Pankaj P, Lole Kavita S
Resumo: Chikungunya virus (CHIKV) is an insect borne virus (genus: Alphavirus) which causes acute febrile illness in humans followed by a prolonged arthralgic disease that affects the joints of the extremities. Re-emergence of the virus in the form of outbreaks in last 6-7 years has posed a serious public health problem. CHIKV has a positive sense single str-ed RNA genome of about 12,000 nt. Open reading frame 1 of the viral genome encodes a polyprotein precursor, nsP1234, which is processed further into different non structural proteins (nsP1, nsP2, nsP3 - nsP4). Sequence based analyses have shown helicase domain at the N-terminus - protease domain at C-terminus of nsP2. A detailed biochemical analysis of NTPase/RNA helicase - 5'-RNA phosphatase activities of recombinant CHIKV-nsP2T protein (containing conserved NTPase/helicase motifs in the N-terminus - partial papain like protease domain at the C-terminus) was carried out. The protein could hydrolyze all NTPs except dTTP - showed better efficiency for ATP, dATP, GTP - dGTP hydrolysis. ATP was the most preferred substrate by the enzyme. CHIKV-nsP2T also showed 5'-triphosphatase (RTPase) activity that specifically removes the ?-phosphate from the 5' end of RNA. Both NTPase - RTPase activities of the protein were completely dependent on Mg(2+) ions. RTPase activity was inhibited by ATP showing sharing of the binding motif by NTP - RNA. Both enzymatic activities were drastically reduced by mutations in the NTP binding motif (GKT) - co-factor, Mg(2+) ion binding motif (DEXX) suggesting that they have a common catalytic site.
Imprenta: PloS One, v. 6, n. 7, p. e22336, 2011
Identificador do objeto digital: 10.1371/journal.pone.0022336
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - DNA ; Chikungunya virus - Genome ; Chikungunya virus - Molecular structure ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya Virus - Virus ; Chikungunya virus - Public health
Data de publicação: 2011
