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Publication Abstract from PubMed

dNTP triphosphohydrolase (TPH) belongs to the histidine/aspartate (HD) superfamily and catalyzes the hydrolysis of dNTPs into 2'-deoxyribonucleoside and inorganic triphosphate. TPHs are required for cellular dNTP homeostasis and DNA replication fidelity and are employed as a host defense mechanism. PA1124 from the pathogenic Pseudomonas aeruginosa bacterium functions as a dGTP and dTTP triphosphohydrolase. To reveal how PA1124 drives dNTP hydrolysis and is regulated, we performed a structural study of PA1124. PA1124 assembles into a hexameric architecture as a trimer of dimers. Each monomer has an interdomain dent where a metal ion is coordinated by conserved histidine and aspartate residues. A structure-based comparative analysis suggests that PA1124 accommodates the dNTP substrate into the interdomain dent near the metal ion. Interestingly, PA1124 interacts with ssDNA, presumably as an allosteric regulator, using a positively charged intersubunit cleft that is generated via dimerization. Furthermore, our phylogenetic analysis highlights similar or distinct oligomerization profiles across the TPH family.

Structural analysis of the dNTP triphosphohydrolase PA1124 from Pseudomonas aeruginosa.,Oh HB, Lee KC, Park SC, Song WS, Yoon SI Biochem Biophys Res Commun. 2022 Jan 22;589:78-84. doi:, 10.1016/j.bbrc.2021.12.002. Epub 2021 Dec 2. PMID:34894560^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.