7u67

Structure of E. coli dGTPase bound to T7 bacteriophage protein Gp1.2 and GTP

spinqualitylabelsall models 7u67, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7u67 is a 12 chain structure with sequence from Escherichia coli str. K-12 substr. MG1655 and Escherichia phage T7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.5Å Ligands: GTP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DGTP_ECOLI dGTPase preferentially hydrolyzes dGTP over the other canonical NTPs.[HAMAP-Rule:MF_00030] Publication Abstract from PubMed Levels of the cellular dNTPs, the direct precursors for DNA synthesis, are important for DNA replication fidelity, cell cycle control, and resistance against viruses. Escherichia coli encodes a dGTPase (2'-deoxyguanosine-5'-triphosphate [dGTP] triphosphohydrolase [dGTPase]; dgt gene, Dgt) that establishes the normal dGTP level required for accurate DNA replication but also plays a role in protecting E. coli against bacteriophage T7 infection by limiting the dGTP required for viral DNA replication. T7 counteracts Dgt using an inhibitor, the gene 1.2 product (Gp1.2). This interaction is a useful model system for studying the ongoing evolutionary virus/host "arms race." We determined the structure of Gp1.2 by NMR spectroscopy and solved high-resolution cryo-electron microscopy structures of the Dgt-Gp1.2 complex also including either dGTP substrate or GTP coinhibitor bound in the active site. These structures reveal the mechanism by which Gp1.2 inhibits Dgt and indicate that Gp1.2 preferentially binds the GTP-bound form of Dgt. Biochemical assays reveal that the two inhibitors use different modes of inhibition and bind to Dgt in combination to yield enhanced inhibition. We thus propose an in vivo inhibition model wherein the Dgt-Gp1.2 complex equilibrates with GTP to fully inactivate Dgt, limiting dGTP hydrolysis and preserving the dGTP pool for viral DNA replication. Mechanism by which T7 bacteriophage protein Gp1.2 inhibits Escherichia coli dGTPase.,Klemm BP, Singh D, Smith CE, Hsu AL, Dillard LB, Krahn JM, London RE, Mueller GA, Borgnia MJ, Schaaper RM Proc Natl Acad Sci U S A. 2022 Sep 13;119(37):e2123092119. doi: , 10.1073/pnas.2123092119. Epub 2022 Sep 6. PMID:36067314 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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