Premium
High‐resolution structure of the Influenza A virus PB2cap binding domain illuminates the changes induced by ligand binding
Author(s) -
Constantinides Amanda,
Gumpper Ryan,
Severin Chelsea,
Luo Ming
Publication year - 2018
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x18000894
Subject(s) - virus , influenza a virus , heterotrimeric g protein , computational biology , ligand (biochemistry) , polymerase , virology , biology , chemistry , receptor , gene , genetics , g protein
In the face of increasing drug resistance and the rapidly increasing necessity for practicality in clinical settings, drugs targeting different viral proteins are needed in order to control influenza A and B. A small molecule that tenaciously adheres to the PB2cap binding domain, part of the heterotrimeric RNA polymerase machinery of influenza A virus and influenza B virus , is a promising drug candidate. Understanding the anatomic behavior of PB2cap upon ligand binding will aid in the development of a more robust inhibitor. In this report, the anatomic behavior of the influenza A virus PB2cap domain is established by solving the crystal structure of native influenza A virus PB2cap at 1.52 Å resolution. By comparing it with the ligand‐bound structure, the dissociation and rotation of the ligand‐binding domain in PB2cap from the C‐terminal domain is identified. This domain movement is present in many PB2cap structures, suggesting its functional relevance for polymerase activity.