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Acta Crystallogr F Struct Biol Commun. 2018 Mar 1;74(Pt 3):122-127. doi: 10.1107/S2053230X18000894. Epub 2018 Feb 26.
High-resolution structure of the Influenza A virus PB2cap binding domain illuminates the changes induced by ligand binding.
Constantinides A1, Gumpper R1, Severin C1, Luo M1.
Author information
Abstract
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.
KEYWORDS:
Influenza A virus; RNA polymerase; cap-snatching; domain movement; high resolution structures; polymerase basic protein 2; transcription
PMID: 29497014 DOI: 10.1107/S2053230X18000894
High-resolution structure of the Influenza A virus PB2cap binding domain illuminates the changes induced by ligand binding.
Constantinides A1, Gumpper R1, Severin C1, Luo M1.
Author information
Abstract
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.
KEYWORDS:
Influenza A virus; RNA polymerase; cap-snatching; domain movement; high resolution structures; polymerase basic protein 2; transcription
PMID: 29497014 DOI: 10.1107/S2053230X18000894