tetano
Editor, Senior Moderator
Acta Crystallogr F Struct Biol Commun. 2018 Mar 1;74(Pt 3):122-127. doi: 10.1107/S2053230X18000894. Epub 2018 Feb 26.
[h=1]High-resolution structure of the Influenza A virus PB2cap binding domain illuminates the changes induced by ligand binding.[/h] Constantinides A[SUP]1[/SUP], Gumpper R[SUP]1[/SUP], Severin C[SUP]1[/SUP], Luo M[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 ? 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.
[h=4]KEYWORDS:[/h] Influenza A virus; RNA polymerase; cap-snatching; domain movement; high resolution structures; polymerase basic protein 2; transcription
PMID: 29497014 DOI: 10.1107/S2053230X18000894
[h=1]High-resolution structure of the Influenza A virus PB2cap binding domain illuminates the changes induced by ligand binding.[/h] Constantinides A[SUP]1[/SUP], Gumpper R[SUP]1[/SUP], Severin C[SUP]1[/SUP], Luo M[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 ? 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.
[h=4]KEYWORDS:[/h] Influenza A virus; RNA polymerase; cap-snatching; domain movement; high resolution structures; polymerase basic protein 2; transcription
PMID: 29497014 DOI: 10.1107/S2053230X18000894