Download MendeleyConformational Polymorphism of m7GTP in Crystal Structure of the PB2 Middle Domain from Human Influenza A Virus
Tsurumura, T., Qiu, H., Yoshida, T., Tsumori, Y., Hatakeyama, D., Kuzuhara, T., Tsuge, H.(2013) PLoS One 8: e82020-e82020
- PubMed: 24312396
- DOI: https://doi.org/10.1371/journal.pone.0082020
- Primary Citation of Related Structures:
3WI0, 3WI1 - PubMed Abstract:
Influenza pandemics with human-to-human transmission of the virus are of great public concern. It is now recognized that a number of factors are necessary for human transmission and virulence, including several key mutations within the PB2 subunit of RNA-dependent RNA polymerase. The structure of the middle domain in PB2 has been revealed with or without m(7)GTP, thus the middle domain is considered to be novel target for structure-based drug design. Here we report the crystal structure of the middle domain of H1N1 PB2 with or without m(7)GTP at 1.9 ? and 2.0 ? resolution, respectively, which has two mutations (P453H, I471T) to increase electrostatic potential and solubility. Here we report the m(7)GTP has unique conformation differ from the reported structure. 7-methyl-guanine is fixed in the pocket, but particularly significant change is seen in ribose and triphosphate region: the buried 7-methyl-guanine indeed binds in the pocket forming by H357, F404, E361 and K376 but the triphosphate continues directly to the outer domain. The presented conformation of m(7)GTP may be a clue for the anti-influenza drug-design.
Organizational Affiliation:
Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kyoto, Japan.
