5u7e | pdb_00005u7e

Apo dihydroneopterin triphosphate pyrophosphohydrolase from E. coli

spinqualitylabelsall models 5u7e, resolution 1.94Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5u7e is a 1 chain structure with sequence from Eco57. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, SO4 Related: 5u7f, 5u7h Gene: nudB, Z2917, ECs2575 (ECO57) Activity: Dihydroneopterin triphosphate diphosphatase, with EC number 3.6.1.67 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [NUDB_ECO57] Catalyzes the hydrolysis of dihydroneopterin triphosphate to dihydroneopterin monophosphate and pyrophosphate. Required for efficient folate biosynthesis. Can also hydrolyze nucleoside triphosphates with a preference for dATP.[UniProtKB:P0AFC0] Publication Abstract from PubMed Dihydroneopterin triphosphate pyrophosphatase (DHNTPase), a member of the Mg2+ dependent Nudix hydrolase superfamily, is the recently-discovered enzyme that functions in the second step of the pterin branch of the folate biosynthetic pathway in E. coli. DHNTPase is of interest because inhibition of enzymes in bacterial folate biosynthetic pathways is a strategy for antibiotic development. We determined crystal structures of DHNTPase with and without activating, Mg2+-mimicking metals Co2+ and Ni2+. Four metal ions, identified by anomalous scattering, and stoichiometrically confirmed in solution by isothermal titration calorimetry, are held in place by Glu56 and Glu60 within the Nudix sequence motif, Glu117, waters, and a sulfate ion, of which the latter is further stabilized by a salt bridge with Lys7. In silico docking of the DHNTP substrate reveals a binding mode in which the pterin ring moiety is nestled in a largely hydrophobic pocket, the beta-phosphate activated for nucleophilic attack overlays with the crystallographic sulfate and is in line with an activated water molecule, and remaining phosphate groups are stabilized by all four identified metal ions. The structures and binding data provide new details regarding DHNTPase metal requirements, mechanism, and suggest a strategy for efficient inhibition. Metal ion coordination in the E. coli Nudix hydrolase dihydroneopterin triphosphate pyrophosphatase: New clues into catalytic mechanism.,Hill SE, Nguyen E, Ukachukwu CU, Freeman DM, Quirk S, Lieberman RL PLoS One. 2017 Jul 25;12(7):e0180241. doi: 10.1371/journal.pone.0180241., eCollection 2017. PMID:28742822 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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