Structural highlights
Function
[PB2_I34A1] Involved in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNA are used to generate primers for viral transcription. Binds the cap of the target pre-RNA which is subsequently cleaved by PB1. May play a role in genome replication (By similarity).
Publication Abstract from PubMed
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 1.9A and 2.0A 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.
Conformational Polymorphism of m(7)GTP 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 PLoS One. 2013 Nov 29;8(11):e82020. doi: 10.1371/journal.pone.0082020. PMID:24312396[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tsurumura T, Qiu H, Yoshida T, Tsumori Y, Hatakeyama D, Kuzuhara T, Tsuge H. Conformational Polymorphism of m(7)GTP in Crystal Structure of the PB2 Middle Domain from Human Influenza A Virus. PLoS One. 2013 Nov 29;8(11):e82020. doi: 10.1371/journal.pone.0082020. PMID:24312396 doi:http://dx.doi.org/10.1371/journal.pone.0082020
