8cga

Structure of Mycobacterium tuberculosis dUTPase delta 133A-137S mutant

spinqualitylabelsall models 8cga, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8cga is a 1 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.3Å Ligands: DUP, GOL, MG, SO4, TRS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DUT_MYCTU This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.[HAMAP-Rule:MF_00116] Publication Abstract from PubMed The dUTPase is a key DNA repair enzyme in Mycobacterium tuberculosis, and it may serve as a novel promising anti-tuberculosis target. Stl repressor from Staphylococcus aureus was shown to bind to and inhibit dUTPases from various sources, and its expression in mycobacterial cells interfered with cell growth. To fine-tune and optimize Stl-induced inhibition of mycobacterial dUTPase, we aimed to decipher the molecular details of this interaction. Structural background of the complex between dUTPase and a truncated Stl lacking the repressor C-terminal homodimerization domain has been described, however, the effects of this truncation of Stl on enzyme binding and inhibition are still not known. Using several independent biophysical, structural and enzyme kinetic methods, here we show that lack of the repressor homodimerization domain strongly perturbs both enzyme binding and inhibition. We also investigated the role of a mycobacteria-specific loop in the Stl-interaction. Our results show that removal of this loop leads to a ten-fold increase in the apparent inhibition constant of Stl. We present a high-resolution three-dimensional structure of mycobacterial dUTPase lacking the genus-specific loop for structural insight. Our present data suggest that potent inhibition of mycobacterial dUTPase by Stl requires the wild-type full-length protein context. The homodimerization domain of the Stl repressor is crucial for efficient inhibition of mycobacterial dUTPase.,Toth ZS, Leveles I, Nyiri K, Nagy GN, Harmat V, Jaroentomeechai T, Ozohanics O, Miller RL, Alvarez MB, Vertessy BG, Benedek A Sci Rep. 2024 Nov 8;14(1):27171. doi: 10.1038/s41598-024-76349-2. PMID:39511242 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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