3wi1

From Proteopedia

P453H/I471T mutant of PB2 middle domain from influenza virus A/Puerto Rico/8/34(H1N1) with m7GTP

Structural highlights

3wi1 is a 1 chain structure with sequence from Influenza A virus (A/Puerto Rico/8/1934(H1N1)). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.931Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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