| RRC ID |
28585
|
| Author |
Tsurumura T, Qiu H, Yoshida T, Tsumori Y, Hatakeyama D, Kuzuhara T, Tsuge H.
|
| Title |
Conformational polymorphism of m7GTP in crystal structure of the PB2 middle domain from human influenza A virus.
|
| Journal |
PLoS One
|
| 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 Å and 2.0 Å 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.
|
| Volume |
8(11)
|
| Pages |
e82020
|
| Published |
2013-1-1
|
| DOI |
10.1371/journal.pone.0082020
|
| PII |
PONE-D-13-36305
|
| PMID |
24312396
|
| PMC |
PMC3843726
|
| MeSH |
Amino Acid Sequence
Crystallography, X-Ray
Humans
Influenza A Virus, H1N1 Subtype / chemistry*
Molecular Conformation
Molecular Sequence Data
Mutation
RNA Cap Analogs / chemistry
RNA Cap Analogs / metabolism*
Sequence Homology, Amino Acid
|
| IF |
2.74
|
| Times Cited |
8
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| DNA material |
pBMSA-PB2 (RDB01969) |
