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Conformational polymorphism of m7GTP in crystal structure of the PB2 middle domain from human influenza A virus.

<div class='caption-title'>Crystal structure of PB2 middle domain (amino acids 318 to 483) of H1N1 from human influenza A virus with or without m7GTP.</div>
<div class='caption-title'>Electron densities of the active sites in stereo view.</div>
<div class='caption-title'>Comparison the m7GTP-bound form in H1N1 (this report) and H3N2 (2VQZ).</div>
Tsurumura T, Qiu H, Yoshida T, Tsumori Y, Hatakeyama D, Kuzuhara T, Tsuge H
OpenAccess logo PLoS One 8 e82020 (2013)
Cited: 6 times
EuropePMC logo PMID: 24312396

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.

Articles - 3wi0 mentioned but not cited (2)

  1. Conformational 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. PLoS One 8 e82020 (2013)
  2. Therapeutic p28 peptide targets essential H1N1 influenza virus proteins: insights from docking and molecular dynamics simulations. Sasidharan S, Gosu V, Shin D, Nath S, Tripathi T, Saudagar P. Mol Divers 25 1929-1943 (2021)


Reviews citing this publication (1)

  1. Structural and Biochemical Analyses on the RNA-dependent RNA Polymerase of Influenza Virus for Development of Novel Anti-influenza Agents. Hatakeyama D. Yakugaku Zasshi 137 205-214 (2017)

Articles citing this publication (3)

  1. Molecular Basis of mRNA Cap Recognition by Influenza B Polymerase PB2 Subunit. Xie L, Wartchow C, Shia S, Uehara K, Steffek M, Warne R, Sutton J, Muiru GT, Leonard VH, Bussiere DE, Ma X. J Biol Chem 291 363-370 (2016)
  2. The crystal structure of the PB2 cap-binding domain of influenza B virus reveals a novel cap recognition mechanism. Liu Y, Yang Y, Fan J, He R, Luo M, Zheng X. J Biol Chem 290 9141-9149 (2015)
  3. The cap-binding site of influenza virus protein PB2 as a drug target. Severin C, Rocha de Moura T, Liu Y, Li K, Zheng X, Luo M. Acta Crystallogr D Struct Biol 72 245-253 (2016)


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