7SZY

High-resolution structure of the nuclease domain from the main replication protein NS1 of Human Parvovirus B19

7SZY の概要

• エントリーDOI: 10.2210/pdb7szy/pdb
• 分子名称: NS1 protein, CITRIC ACID (3 entities in total)
• 機能のキーワード: nuclease domain, viral origin of replication binding domain, parvovirus, double-stranded dna binding, dna nicking, viral protein
• 由来する生物種: Human parvovirus B19
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20076.90

構造登録者

Horton, N.C. (登録日: 2021-11-29, 公開日: 2022-03-30, 最終更新日: 2023-10-18)

主引用文献

Sanchez, J.L.,Ghadirian, N.,Horton, N.C.
High-Resolution Structure of the Nuclease Domain of the Human Parvovirus B19 Main Replication Protein NS1.
J.Virol., 96:e0216421-e0216421, 2022

PubMed Abstract: Two new structures of the N-terminal domain of the main replication protein, NS1, of human parvovirus B19 (B19V) are presented here. This domain (NS1-nuc) plays an important role in the "rolling hairpin" replication of the single-stranded B19V DNA genome, recognizing origin of replication sequences in double-stranded DNA, and cleaving (i.e., nicking) single-stranded DNA at a nearby site known as the terminal resolution site (trs). The three-dimensional structure of NS1-nuc is well conserved between the two forms, as well as with a previously solved structure of a sequence variant of the same domain; however, it is shown here at a significantly higher resolution (2.4 Å). Using structures of NS1-nuc homologues bound to single- and double-stranded DNA, models for DNA recognition and nicking by B19V NS1-nuc are presented that predict residues important for DNA cleavage and for sequence-specific recognition at the viral origin of replication. The high-resolution structure of the DNA binding and cleavage domain of the main replicative protein, NS1, from the human-pathogenic virus human parvovirus B19 is presented here. Included also are predictions of how the protein recognizes important sequences in the viral DNA which are required for viral replication. These predictions can be used to further investigate the function of this protein, as well as to predict the effects on viral viability due to mutations in the viral protein and viral DNA sequences. Finally, the high-resolution structure facilitates structure-guided drug design efforts to develop antiviral compounds against this important human pathogen.

PubMed: 35435730
DOI: 10.1128/jvi.02164-21

実験手法

X-RAY DIFFRACTION (2.4 Å)