7PWJ

dUTPase from human in complex with Stl

これはPDB形式変換不可エントリーです。

7PWJ の概要

• エントリーDOI: 10.2210/pdb7pwj/pdb
• 分子名称: Orf20, Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: dutpase, dutp, human, dna, structural protein
• 由来する生物種: Staphylococcus aureus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 104404.09

構造登録者

Sanz-Frasquet, C.,Marina, A. (登録日: 2021-10-06, 公開日: 2022-12-28, 最終更新日: 2024-02-07)

主引用文献

Sanz-Frasquet, C.,Ciges-Tomas, J.R.,Alite, C.,Penades, J.R.,Marina, A.
The Bacteriophage-Phage-Inducible Chromosomal Island Arms Race Designs an Interkingdom Inhibitor of dUTPases.
Microbiol Spectr, 11:e0323222-e0323222, 2023

PubMed Abstract: Stl, the master repressor of the Staphylococcus aureus pathogenicity islands (SaPIs), targets phage-encoded proteins to derepress and synchronize the SaPI and the helper phage life cycles. To activate their cycle, some SaPI Stls target both phage dimeric and phage trimeric dUTPases (Duts) as antirepressors, which are structurally unrelated proteins that perform identical functions for the phage. This intimate link between the SaPI's repressor and the phage inducer has imposed an evolutionary optimization of Stl that allows the interaction with Duts from unrelated organisms. In this work, we structurally characterize this sophisticated mechanism of specialization by solving the structure of the prototypical SaPIbov1 Stl in complex with a prokaryotic and a eukaryotic trimeric Dut. The heterocomplexes with Mycobacterium tuberculosis and Homo sapiens Duts show the molecular strategy of Stl to target trimeric Duts from different kingdoms. Our structural results confirm the participation of the five catalytic motifs of trimeric Duts in Stl binding, including the C-terminal flexible motif V that increases the affinity by embracing Stl. and analyses with a monomeric Dut support the capacity of Stl to recognize this third family of Duts, confirming this protein as a universal Dut inhibitor in the different kingdoms of life. Stl, the Staphylococcus aureus pathogenicity island (SaPI) master repressor, targets phage-encoded proteins to derepress and synchronize the SaPI and the helper phage life cycles. This fascinating phage-SaPI arms race is exemplified by the Stl from SaPIbov1 which targets phage dimeric and trimeric dUTPases (Duts), structurally unrelated proteins with identical functions in the phages. By solving the structure of the Stl in complex with a prokaryotic (M. tuberculosis) and a eukaryotic (human) trimeric Dut, we showed that Stl has developed a sophisticated substrate mimicry strategy to target trimeric Duts. Since all these Duts present identical catalytic mechanisms, Stl is able to interact with Duts from different kingdoms. In addition, modeling with monomeric Dut supports the capacity of Stl to recognize this third family of Duts, confirming this protein as a universal Dut inhibitor.

PubMed: 36622213
DOI: 10.1128/spectrum.03232-22

実験手法

X-RAY DIFFRACTION (1.944 Å)