4lrl | pdb_00004lrl

Structure of an Enterococcus Faecalis HD-domain protein complexed with dGTP and dTTP

spinqualitylabelsall models 4lrl, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4lrl is a 4 chain structure with sequence from Enterococcus faecalis V583. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.35Å Ligands: DGT, MLI, NI, TRS, TTP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q836G9_ENTFA Publication Abstract from PubMed EF1143 from Enterococcus faecalis, a life-threatening pathogen that is resistant to common antibiotics, is a homo-tetrameric deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase (dNTPase), converting dNTPs into the deoxyribonucleosides and triphosphate. The dNTPase activity of EF1143 is regulated by canonical dNTPs, which simultaneously act as substrates and activity modulators. Previous crystal structures of apo-EF1143 and the protein bound to both dGTP and dATP suggested allosteric regulation of its enzymatic activity by dGTP binding at four identical allosteric sites. However, whether and how other canonical dNTPs regulate the enzyme activity was not defined. Here, we present the crystal structure of EF1143 in complex with dGTP and dTTP. The new structure reveals that the tetrameric EF1143 contains four additional secondary allosteric sites adjacent to the previously identified dGTP-binding primary regulatory sites. Structural and enzyme kinetic studies indicate that dGTP binding to the first allosteric site, with nanomolar affinity, is a prerequisite for substrate docking and hydrolysis. Then, the presence of a particular dNTP in the second site either enhances or inhibits the dNTPase activity of EF1143. Our results provide the first mechanistic insight into dNTP-mediated regulation of dNTPase activity. Mechanisms of Allosteric Activation and Inhibition of the Deoxyribonucleoside Triphosphate Triphosphohydrolase from Enterococcus faecalis.,Vorontsov II, Wu Y, Delucia M, Minasov G, Mehrens J, Shuvalova L, Anderson WF, Ahn J J Biol Chem. 2014 Jan 31;289(5):2815-24. doi: 10.1074/jbc.M113.524207. Epub 2013 , Dec 12. PMID:24338016 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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